Signature for diagnosis of bacterial vs viral infections

ABSTRACT

This disclosure provides a gene expression-based method for determining whether a subject has a viral infection or a bacterial infection. A kit for performing the method is also provided.

CROSS-REFERENCING

This application claims the benefit of provisional application Ser. No. 62/823,460, filed on Mar. 25, 2019, which application is incorporated by reference herein in its entirety for all purposes.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

This invention was made with Government support under contracts AI057229 and AI109662 awarded by the National Institutes of Health. The Government has certain rights in the invention.

BACKGROUND

Early and accurate diagnosis of infection is key to improving patient outcomes and reducing antibiotic resistance. The mortality rate of bacterial sepsis increases 8% for each hour by which antibiotics are delayed; however, giving antibiotics to patients without bacterial infections increases rates of morbidity and antimicrobial resistance. The rate of inappropriate antibiotic prescriptions in the hospital setting is estimated at 30-50%, and would be aided by improved diagnostics. Strikingly, close to 95% of patients given antibiotics for suspected enteric fever have negative cultures. There is currently no gold-standard point of care diagnostic that can broadly determine the presence and type of infection. Thus, the White House has established a National Action Plan for Combating Antibiotic-Resistant Bacteria, which called for “point-of-need diagnostic tests to distinguish rapidly between bacterial and viral infections”.

While come PCR-based molecular diagnostics can profile pathogens directly from a blood culture, such methods rely on the presence of adequate numbers of pathogens in the blood. Moreover, they are limited to detecting a discrete range of pathogens. As a result, there is growing interest in molecular diagnostics that profile the host gene response. These include diagnostics that can distinguish the presence of infection as compared to inflamed but non-infected patients. Overall, while great promise has been shown in this field, no host gene expression infection diagnostic has yet made it into clinical practice.

There remains a need for sensitive and specific diagnostic tests that can distinguish between bacterial and viral infections.

SUMMARY

Patients can be classified as having a viral infection or bacterial infection based on the expression of eight genes: by JUP, SUCLG2, IFI27, FCER1A, HESX1, SMARCD3, ICAM1, and EBI3. Increased JUP, SUCLG2, IFI27, FCER1A, HESX1 expression indicates that the subject has a viral infection and increased SMARCD3, ICAM1, EBI3 indicates that the subject has a bacterial infection.

In some embodiments a method of analyzing a sample is provided. This method may comprise: (a) obtaining a sample of RNA from a subject; and (b) measuring the amount of RNA transcripts encoded by JUP, SUCLG2, IFI27, FCER1A, HESX1, SMARCD3, ICAM1, and EBI3 in the sample, to produce gene expression data. This method may further comprise, based on the gene expression data, providing a report indicating whether the subject has a viral infection or a bacterial infection, wherein: (i) increased JUP, SUCLG2, IFI27, FCER1A, HESX1 expression indicates that the subject has a viral infection; and (ii) increased SMARCD3, ICAM1, EBI3 indicates that the subject has a bacterial infection.

In some embodiments, a method of treatment is provided. In these embodiments, the method may comprise (a) receiving a report indicating whether the subject has a viral infection or a bacterial infection, wherein the report is based on the gene expression data obtained by measuring the amount of RNA transcripts encoded by JUP, SUCLG2, IFI27, FCER1A, HESX1, SMARCD3, ICAM1, and EBI3, and (b) identifying the patient as having increased JUP, SUCLG2, IFI27, and FCER1A, and HESX1 expression, and treating the subject with anti-viral therapy; or (c) identifying the patient as having increased SMARCD3, ICAM1, EBI3 expression; and treating the subject with an anti-bacterial therapy.

Kits for performing the method are also provided.

BRIEF DESCRIPTION OF THE FIGURES

The invention is best understood from the following detailed description when read in conjunction with the accompanying drawings. It is emphasized that, according to common practice, the various features of the drawings are not to-scale. On the contrary, the dimensions of the various features are arbitrarily expanded or reduced for clarity. Included in the drawings are the following figures:

FIG. 1 provides an overview of MANATEE.

FIG. 2 provides an 8-gene signature that distinguishes viral infections from intracellular and extracellular bacterial infections with high accuracy in the discovery and held-out validation data.

FIG. 3 provides an 8-gene signature that distinguishes viral infections from intracellular and extracellular bacterial infections with high accuracy in independent whole blood datasets.

FIG. 4 provides an 8-gene signature that distinguishes viral infections from intracellular and extracellular bacterial infections with high accuracy in independent PBMC datasets.

FIG. 5 provides an 8-gene signature that distinguishes viral infections from intracellular and extracellular bacterial infections with high accuracy in a prospectively enrolled cohort of patients with bacterial or viral infections in Nepal.

DETAILED DESCRIPTION

The practice of the present invention will employ, unless otherwise indicated, conventional methods of pharmacology, chemistry, biochemistry, recombinant DNA techniques and immunology, within the skill of the art. Such techniques are explained fully in the literature. See, e.g., Handbook of Experimental Immunology, Vols. I-IV (D. M. Weir and C. C. Blackwell eds., Blackwell Scientific Publications); A. L. Lehninger, Biochemistry (Worth Publishers, Inc., current addition); Sambrook, et al., Molecular Cloning: A Laboratory Manual (2nd Edition, 1989); Methods In Enzymology (S. Colowick and N. Kaplan eds., Academic Press, Inc.).

All publications, patents and patent applications cited herein, whether supra or infra, are hereby incorporated by reference in their entireties.

Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, some potential and preferred methods and materials are now described. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited. It is understood that the present disclosure supersedes any disclosure of an incorporated publication to the extent there is a contradiction.

As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present invention. Any recited method can be carried out in the order of events recited or in any other order which is logically possible.

It must be noted that, as used in this specification and the appended claims, the singular forms “a”, “an” and “the” include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to “an agonist” includes a mixture of two or more such agonists, and the like.

The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed.

As noted above, a method of analyzing a sample is provided. In some embodiments the method comprises (a) obtaining a sample of RNA from a subject; and (b) measuring the amount of RNA transcripts encoded by JUP, SUCLG2, IFI27, FCER1A, HESX1, SMARCD3, ICAM1, and EBI3 in the sample, to produce gene expression data. The method may be used in a variety of diagnostic and therapeutic methods, as described below.

Diagnostic Methods

As noted above, the method may be used to determine if a subject has a viral infection or bacterial infection. In some embodiments, the method may comprise: (a) obtaining a sample of RNA from a subject; (b) measuring the amount of RNA transcripts encoded by JUP, SUCLG2, IFI27, FCER1A, HESX1, SMARCD3, ICAM1, and EBI3 in the sample, to produce gene expression data and (c) providing a report indicating whether the subject has a viral infection or a bacterial infection, wherein: (i) increased JUP, SUCLG2, IFI27, FCER1A, HESX1 expression indicates that the subject has a viral infection; and (ii) increased SMARCD3, ICAM1, EBI3 indicates that the subject has a bacterial infection.

The measuring step can be done using any suitable method. For example, the amount of the RNA transcripts in the sample may be measured by RNA-seq (see, e.g., Morin et al BioTechniques 2008 45: 81-94; Wang et al 2009 Nature Reviews Genetics 10: 57-63), RT-PCR (Freeman et al BioTechniques 1999 26: 112-22, 124-5), or by labeling the RNA or cDNA made from the same and hybridizing the labeled RNA or cDNA to an array. An array may contain spatially-addressable or optically-addressable sequence-specific oligonucleotide probes that specifically hybridize to transcripts being measured, or cDNA made from the same. Spatially-addressable arrays (which are commonly referred to as “microarrays” in the art) are described in, e.g., Sealfon et al (see, e.g., Methods Mol Biol. 2011; 671:3-34). Optically-addressable arrays (which are commonly referred to as “bead arrays” in the art) use beads that internally dyed with fluorophores of differing colors, intensities and/or ratios such that the beads can be distinguished from each other, where the beads are also attached to an oligonucleotide probe. Exemplary bead-based assays are described in Dupont et al (J. Reprod Immunol. 2005 66:175-91) and Khalifian et al (J Invest Dermatol. 2015 135: 1-5). The abundance of transcripts in a sample can also be analyzed by quantitative RT-PCR or isothermal amplification method such as those described in Gao et al (J. Virol Methods. 2018 255: 71-75), Pease et al (Biomed Microdevices (2018) 20: 56) or Nixon et (Biomol. Det. and Quant 2014 2: 4-10), for example. Many other methods for measuring the amount of an RNA transcript in a sample are known in the art.

The sample of RNA obtained from the subject may comprise RNA isolated from whole blood, white blood cells, peripheral blood mononuclear cells (PBMC), neutrophils or buffy coat, for example. Methods for making total RNA, polyA+ RNA, RNA that has been depleted for abundant transcripts, and RNA that has been enriched for the transcripts being measured are well known (see, e.g., Hitchen et al J Biomol Tech. 2013 24: S43-S44). If the method involves making cDNA from the RNA, then the cDNA may be made using an oligo(d)T primer, a random primer or a population of gene-specific primers that hybridize to the transcripts being analyzed.

In measuring the transcript, the absolute amount of each transcript may be determined, or the amount of each transcript relative to one or more control transcript may be determined. Whether the amount of a transcript is increased or decreased may be in relation to the amount of the transcript (e.g., the average amount of the transcript) in control samples (e.g., in blood samples collected from a population of at least 100, at least 200, or at least 500 subjects that are known or not known to have viral and/or bacterial infections).

In some embodiments, the method may comprise providing a report indicating whether the subject has a viral or bacterial infection based on the measurements of the amounts of the transcripts. In some embodiments, this step may involve calculating a score based on the weighted amounts of each of the transcripts, where the scores correlates with the phenotype and can be a number such as a probability, likelihood or score out of 10, for example. In these embodiments, the method may comprise inputting the amounts of each of the transcripts into one or more algorithms, executing the algorithms, and receiving a score for each phenotype based on the calculations. In these embodiments, other measurements from the subject, e.g., whether the subject is male, the age of the subject, white blood cell count, neutrophils count, band count, lymphocyte count, monocyte count, whether the subject is immunosuppressed, and/or whether there are Gram-negative bacteria present, etc., may be input into the algorithm.

In some embodiments, the method may involve creating the report e.g., in an electronic form, and forwarding the report to a doctor or other medical professional to help identify a suitable course of action, e.g., to identify a suitable therapy for the subject. The report may be used along with other metrics as a diagnostic to determine whether the subject has a viral of bacterial infection.

In any embodiment, report can be forwarded to a “remote location”, where “remote location,” means a location other than the location at which the image is examined. For example, a remote location could be another location (e.g., office, lab, etc.) in the same city, another location in a different city, another location in a different state, another location in a different country, etc. As such, when one item is indicated as being “remote” from another, what is meant is that the two items can be in the same room but separated, or at least in different rooms or different buildings, and can be at least one mile, ten miles, or at least one hundred miles apart. “Communicating” information references transmitting the data representing that information as electrical signals over a suitable communication channel (e.g., a private or public network). “Forwarding” an item refers to any means of getting that item from one location to the next, whether by physically transporting that item or otherwise (where that is possible) and includes, at least in the case of data, physically transporting a medium carrying the data or communicating the data. Examples of communicating media include radio or infra-red transmission channels as well as a network connection to another computer or networked device, and the internet or including email transmissions and information recorded on websites and the like. In certain embodiments, the report may be analyzed by an MD or other qualified medical professional, and a report based on the results of the analysis of the image may be forwarded to the subject from which the sample was obtained.

In computer-related embodiments, a system may include a computer containing a processor, a storage component (i.e., memory), a display component, and other components typically present in general purpose computers. The storage component stores information accessible by the processor, including instructions that may be executed by the processor and data that may be retrieved, manipulated or stored by the processor.

The storage component includes instructions for determining whether the subject has a viral or bacterial infection using the measurements described above as inputs. The computer processor is coupled to the storage component and configured to execute the instructions stored in the storage component in order to receive patient data and analyze patient data according to one or more algorithms. The display component may display information regarding the diagnosis of the patient.

The storage component may be of any type capable of storing information accessible by the processor, such as a hard-drive, memory card, ROM, RAM, DVD, CD-ROM, USB Flash drive, write-capable, and read-only memories. The processor may be any well-known processor, such as processors from Intel Corporation. Alternatively, the processor may be a dedicated controller such as an ASIC.

The instructions may be any set of instructions to be executed directly (such as machine code) or indirectly (such as scripts) by the processor. In that regard, the terms “instructions,” “steps” and “programs” may be used interchangeably herein. The instructions may be stored in object code form for direct processing by the processor, or in any other computer language including scripts or collections of independent source code modules that are interpreted on demand or compiled in advance.

Data may be retrieved, stored or modified by the processor in accordance with the instructions. For instance, although the diagnostic system is not limited by any particular data structure, the data may be stored in computer registers, in a relational database as a table having a plurality of different fields and records, XML documents, or flat files. The data may also be formatted in any computer-readable format such as, but not limited to, binary values, ASCII or Unicode. Moreover, the data may comprise any information sufficient to identify the relevant information, such as numbers, descriptive text, proprietary codes, pointers, references to data stored in other memories (including other network locations) or information which is used by a function to calculate the relevant data.

Therapeutic Methods

Therapeutic methods are also provided. In some embodiments, these methods may comprise identifying a subject as having a viral infection or a bacterial infection using the methods described above, and treating a subject based on whether the subject is indicated as having a viral infection or bacterial infection. In some embodiments, this method may comprise receiving a report indicating whether the subject has a viral infection or a bacterial infection, wherein the report is based on the gene expression data obtained by measuring the amount of RNA transcripts encoded by JUP, SUCLG2, IFI27, FCER1A, HESX1, SMARCD3, ICAM1, and EBI3, and treating a subject based on whether the subject is indicated as having an viral infection or bacterial infection. In some embodiments the method may comprise: (a) identifying the patient as having increased JUP, SUCLG2, IFI27, and FCER1A, and HESX1 expression, and treating the subject with anti-viral therapy; or (b) identifying the patient as having increased SMARCD3, ICAM1, EBI3 expression, and treating the subject with an anti-bacterial therapy.

A subject indicated as having a viral infection may be treated by administering a therapeutically effective dose of an antiviral agent, such as a broad-spectrum antiviral agent, an antiviral vaccine, a neuraminidase inhibitor (e.g., zanamivir (Relenza) and oseltamivir (Tamiflu)), a nucleoside analogue (e.g., acyclovir, zidovudine (AZT), and lamivudine), an antisense antiviral agent (e.g., phosphorothioate antisense antiviral agents (e.g., Fomivirsen (Vitravene) for cytomegalovirus retinitis), morpholino antisense antiviral agents), an inhibitor of viral uncoating (e g, Amantadine and rimantadine for influenza, Pleconaril for rhinoviruses), an inhibitor of viral entry (e.g., Fuzeon for HIV), an inhibitor of viral assembly (e.g., Rifampicin), or an antiviral agent that stimulates the immune system (e.g., interferons). Exemplary antiviral agents include Abacavir, Aciclovir, Acyclovir, Adefovir, Amantadine, Amprenavir, Ampligen, Arbidol, Atazanavir, Atripla (fixed dose drug), Balavir, Cidofovir, Combivir (fixed dose drug), Dolutegravir, Darunavir, Delavirdine, Didanosine, Docosanol, Edoxudine, Efavirenz, Emtricitabine, Enfuvirtide, Entecavir, Ecoliever, Famciclovir, Fixed dose combination (antiretroviral), Fomivirsen, Fosamprenavir, Foscarnet, Fosfonet, Fusion inhibitor, Ganciclovir, Ibacitabine, Imunovir, Idoxuridine, Imiquimod, Indinavir, Inosine, Integrase inhibitor, Interferon type III, Interferon type II, Interferon type I, Interferon, Lamivudine, Lopinavir, Loviride, Maraviroc, Moroxydine, Methisazone, Nelfinavir, Nevirapine, Nexavir, Nitazoxanide, Nucleoside analogues, Novir, Oseltamivir (Tamiflu), Peginterferon alfa-2a, Penciclovir, Peramivir, Pleconaril, Podophyllotoxin, Protease inhibitor, Raltegravir, Reverse transcriptase inhibitor, Ribavirin, Rimantadine, Ritonavir, Pyramidine, Saquinavir, Sofosbuvir, Stavudine, Synergistic enhancer (antiretroviral), Telaprevir, Tenofovir, Tenofovir disoproxil, Tipranavir, Trifluridine, Trizivir, Tromantadine, Truvada, Valaciclovir (Valtrex), Valganciclovir, Vicriviroc, Vidarabine, Viramidine, Zalcitabine, Zanamivir (Relenza), and Zidovudine.

A subject indicated as having a bacterial infection may be treated by administering a therapeutically effective dose of an antibiotic. Antibiotics may include broad spectrum, bactericidal, or bacteriostatic antibiotics. Exemplary antibiotics include aminoglycosides such as Amikacin, Amikin, Gentamicin, Garamycin, Kanamycin, Kantrex, Neomycin, Neo-Fradin, Netilmicin, Netromycin, Tobramycin, Nebcin, Paromomycin, Humatin, Streptomycin, Spectinomycin(Bs), and Trobicin; ansamycins such as Geldanamycin, Herbimycin, Rifaximin, and Xifaxan; carbacephems such as Loracarbef and Lorabid; carbapenems such as Ertapenem, Invanz, Doripenem, Doribax, Imipenem/Cilastatin, Primaxin, Meropenem, and Merrem; cephalosporins such as Cefadroxil, Duricef, Cefazolin, Ancef, Cefalotin or Cefalothin, Keflin, Cefalexin, Keflex, Cefaclor, Distaclor, Cefamandole, Mandol, Cefoxitin, Mefoxin, Cefprozil, Cefzil, Cefuroxime, Ceftin, Zinnat, Cefixime, Cefdinir, Cefditoren, Cefoperazone, Cefotaxime, Cefpodoxime, Ceftazidime, Ceftibuten, Ceftizoxime, Ceftriaxone, Cefepime, Maxipime, Ceftaroline fosamil, Teflaro, Ceftobiprole, and Zeftera; glycopeptides such as Teicoplanin, Targocid, Vancomycin, Vancocin, Telavancin, Vibativ, Dalbavancin, Dalvance, Oritavancin, and Orbactiv; lincosamides such as Clindamycin, Cleocin, Lincomycin, and Lincocin; lipopeptides such as Daptomycin and Cubicin; macrolides such as Azithromycin, Zithromax, Sumamed, Xithrone, Clarithromycin, Biaxin, Dirithromycin, Dynabac, Erythromycin, Erythocin, Erythroped, Roxithromycin, Troleandomycin, Tao, Telithromycin, Ketek, Spiramycin, and Rovamycine; monobactams such as Aztreonam and Azactam; nitrofurans such as Furazolidone, Furoxone, Nitrofurantoin, Macrodantin, and Macrobid; oxazolidinones such as Linezolid, Zyvox, VRSA, Posizolid, Radezolid, and Torezolid; penicillins such as Penicillin V, Veetids (Pen-Vee-K), Piperacillin, Pipracil, Penicillin G, Pfizerpen, Temocillin, Negaban, Ticarcillin, and Ticar; penicillin combinations such as Amoxicillin/clavulanate, Augmentin, Ampicillin/sulbactam, Unasyn, Piperacillin/tazobactam, Zosyn, Ticarcillin/clavulanate, and Timentin; polypeptides such as Bacitracin, Colistin, Coly-Mycin-S, and Polymyxin B; quinolones/fluoroquinolones such as Ciprofloxacin, Cipro, Ciproxin, Ciprobay, Enoxacin, Penetrex, Gatifloxacin, Tequin, Gemifloxacin, Factive, Levofloxacin, Levaquin, Lomefloxacin, Maxaquin, Moxifloxacin, Avelox, Nalidixic acid, NegGram, Norfloxacin, Noroxin, Ofloxacin, Floxin, Ocuflox Trovafloxacin, Trovan, Grepafloxacin, Raxar, Sparfloxacin, Zagam, Temafloxacin, and Omniflox; sulfonamides such as Amoxicillin, Novamox, Amoxil, Ampicillin, Principen, Azlocillin, Carbenicillin, Geocillin, Cloxacillin, Tegopen, Dicloxacillin, Dynapen, Flucloxacillin, Floxapen, Mezlocillin, Mezlin, Methicillin, Staphcillin, Nafcillin, Unipen, Oxacillin, Prostaphlin, Penicillin G, Pentids, Mafenide, Sulfamylon, Sulfacetamide, Sulamyd, Bleph-10, Sulfadiazine, Micro-Sulfon, Silver sulfadiazine, Silvadene, Sulfadimethoxine Di-Methox, Albon, Sulfamethizole, Thiosulfil Forte, Sulfamethoxazole, Gantanol, Sulfanilimide, Sulfasalazine, Azulfidine, Sulfisoxazole, Gantrisin, Trimethoprim-Sulfamethoxazole (Co-trimoxazole) (TMP-SMX), Bactrim, Septra, Sulfonamidochrysoidine, and Prontosil; tetracyclines such as Demeclocycline, Declomycin, Doxycycline, Vibramycin, Minocycline, Minocin, Oxytetracycline, Terramycin, Tetracycline and Sumycin, Achromycin V, and Steclin; drugs against mycobacteria such as Clofazimine, Lamprene, Dapsone, Avlosulfon, Capreomycin, Capastat, Cycloserine, Seromycin, Ethambutol, Myambutol, Ethionamide, Trecator, Isoniazid, I.N.H., Pyrazinamide, Aldinamide, Rifampicin, Rifadin, Rimactane, Rifabutin, Mycobutin, Rifapentine, Priftin, and Streptomycin; others antibiotics such as Arsphenamine, Salvarsan, Chloramphenicol, Chloromycetin, Fosfomycin, Monurol, Monuril, Fusidic acid, Fucidin, Metronidazole, Flagyl, Mupirocin, Bactroban, Platensimycin, Quinupristin/Dalfopristin, Synercid, Thiamphenicol, Tigecycline, Tigacyl, Tinidazole, Tindamax Fasigyn, Trimethoprim, Proloprim, and Trimpex.

Methods for administering and dosages for administering the therapeutics listed above are known in the art or can be derived from the art.

Kits

Also provided by this disclosure are kits for practicing the subject methods, as described above. In some embodiments, the kit may contain reagents for measuring the amount of RNA transcripts encoded by JUP, SUCLG2, IFI27, FCER1A, HESX1, SMARCD3, ICAM1, and EBI3. In some embodiments, the kit may comprise, for each RNA transcript, a sequence-specific oligonucleotide that hybridizes to the transcript. In some embodiments, the sequence-specific oligonucleotide may be biotinylated and/or labeled with an optically-detectable moiety. In some embodiments, the kit may comprise, for each RNA transcript, a pair of PCR primers that amplify a sequence from the RNA transcript, or cDNA made from the same. In some embodiments, the kit may comprise an array of oligonucleotide probes, wherein the array comprises, for each RNA transcript, at least one sequence-specific oligonucleotide that hybridizes to the transcript. The oligonucleotide probes may be spatially addressable on the surface of a planar support, or tethered to optically addressable beads, for example.

In embodiments in which a quantitative isothermal amplification method is used, the kit may comprise reagents comprise multiple reaction vessels, each vessel comprising at least one (e.g., 2, 3, 4, 5, or 6) sequence-specific isothermal amplification primer that hybridizes to a single transcript, e.g., a transcript from a single gene selected from JUP, SUCLG2, IFI27, FCER1A, HESX1, SMARCD3, ICAM1, and EBI3, or cDNA made from the same. As such, in some embodiments, the kit may contain at least 8 reaction vessels, where each reaction vessels contain one or more primers for detection of an RNA transcript encoded by a single gene. In some embodiments, the kit may contain reagents for measuring the amount of up to a total of 30 or 50 RNA transcripts.

In some embodiments, the kit may contain reagents for measuring the amount of RNA transcripts of a set of any number of genes (e.g., at least 2, at least 3, at least 4, at least 5, at least 6, or at least 7 genes, up to 30 or 50 genes), where the set of genes includes any pair of genes listed in Table 2 as well as optionally other genes (e.g., at least 2, at least 3, at least 4, at least 5, at least 6, or at least 7 other genes) that independently are or are not listed on Table 1. For example, the kit may comprise, for each RNA transcript, a pair of PCR primers that amplify a sequence from the RNA transcript, or cDNA made from the same.

The various components of the kit may be present in separate containers or certain compatible components may be precombined into a single container, as desired.

In addition to the above-mentioned components, the subject kit may further include instructions for using the components of the kit to practice the subject method.

Additional Embodiments

In any embodiment, the method can be practiced by measuring the amount of RNA transcripts encoded by than the eight listed genes, e.g., by measuring the amount of RNA transcripts encoded by 2, 3, 4, 5, 6, or 7 of the listed genes. The total number of transcripts measured in some embodiments may be 30 or 50 RNA in some embodiments.

In addition, other genes can be analyzed in addition to the eight listed genes or subset thereof. For example, in any embodiment, the method may further comprise measuring the amount of RNA transcripts of other genes listed in Table 1 below.

In some embodiments, the method may be practiced by measuring the amount of RNA transcripts of a set of any number of genes (e.g., at least 2, at least 3, at least 4, at least 5, at least 6, or at least 7 genes, up to 30 or 50 genes), where the set of genes includes any pair of genes listed in Table 2 as well as optionally other genes (e.g., at least 2, at least 3, at least 4, at least 5, at least 6, or at least 7 other genes) that are independently listed or not listed in Table 1.

In some embodiments, the method may further comprise measuring the amount of RNA transcripts encoded by CEACAM1, ZDHHC19, C9orf95, GNA15, BATF, C3AR1, KIAA1370, TGFBI, MTCH1, RPGRIP1, and HLA-DPB1 in addition to the listed genes. In these embodiments, increased expression of the CEACAM1, ZDHHC19, C9orf95, GNA15, BATF, and C3AR1 biomarkers and decreased expression of the KIAA1370, TGFBI, MTCH1, RPGRIP1, and HLA-DPB1 indicate that the subject has sepsis as described in WO2016145426. Thus, the present method can be used as an integrated decision model for the treatment of both bacterial and viral infections.

Examples

The following examples are put forth so as to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the present invention and are not intended to limit the scope of what the inventors regard as their invention nor are they intended to represent that the experiments below are all or the only experiments performed. Efforts have been made to ensure accuracy with respect to numbers used (e.g. amounts, temperature, etc.) but some experimental errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, molecular weight is weight average molecular weight, temperature is in degrees Celsius, and pressure is at or near atmospheric. Standard abbreviations may be used, e.g., room temperature (RT); base pairs (bp); kilobases (kb); picoliters (pl); seconds (s or sec); minutes (m or min); hours (h or hr); days (d); weeks (wk or wks); nanoliters (nl); microliters (ul); milliliters (ml); liters (L); nanograms (ng); micrograms (ug); milligrams (mg); grams ((g), in the context of mass); kilograms (kg); equivalents of the force of gravity ((g), in the context of centrifugation); nanomolar (nM); micromolar (uM), millimolar (mM); molar (M); amino acids (aa); kilobases (kb); base pairs (bp); nucleotides (nt); intramuscular (i.m.); intraperitoneal (i.p.); subcutaneous (s.c.); and the like.

Materials and Methods

Systematic Datasets Search

A systematic search was performed in NIH Gene Expression Omnibus (GEO) and European Bioinformatics Institute (EBI) ArrayExpress for public human microarray genome-wide expression studies of pneumonia or other respiratory infections. Datasets were excluded if they (i) were nonclinical, (ii) were performed using tissues other than whole blood or PBMCs, (iii) did not have at least 4 healthy samples, or (iv) did not have sufficient pathogen labels to identify whether the causal agent was bacterial or viral.

All microarray data were renormalized from raw data (when available) using standard methods. Affymetrix arrays were normalized using GC robust multiarray average (gcRMA) (on arrays with mismatch probes) or RMA. Illumina, Agilent, GE, and other commercial arrays were normalized via normal-exponential background correction followed by quantile normalization. Custom arrays were not renormalized and were used as is. Data were log₂-transformed, and a fixed-effect model was used to summarize probes to genes within each study. Within each study, cohorts assayed with different microarray types were treated as independent.

COCONUT Conormalization

Out of 43 datasets that matched inclusion criteria and profiled respiratory infections, only 12 of these datasets contained both bacterial and viral infections, and only a single one contained intracellular bacterial, extracellular bacterial, and viral infections. Because of the difference in background measurements for these different arrays (owing to the use of different platforms), it is difficult to conduct analyses between all 43 datasets without getting significantly skewed results due to the batch effects. In order to make use of these data, Combat CO-Normalization Using conTrols (COCONUT)², which allows for co-normalization of expression data without changing the distribution of genes between studies and without any bias towards sample diagnosis, was used. It applies a modified version of the ComBat empirical Bayes normalization method²⁶ that only assumes an equal distribution between control samples. Briefly, the healthy controls from each cohort undergo ComBat conormalization without covariates, and the ComBat estimated parameters are acquired for each dataset's healthy samples. These parameters are then applied to the diseased samples in each dataset, which causes all samples to assume the same background distribution while still retaining the relative distance between healthy and diseased samples in each dataset.

Calculation of Signature Score

A previously described signature score^(1,2,5,24,25) was used to perform disease classification. The signature score (S_(i)) is calculated as the geometric mean of the genes that are positively correlated with the response variable (in this case, bacterial infections) minus the geometric mean of the negatively correlated genes (Eq. 1).

$\begin{matrix} {S_{i} = {\left( {\prod\limits_{geneepos}{x_{i}({gene})}} \right)^{\frac{1}{{pos}}} - \left( {\prod\limits_{geneeneg}{x_{i}({gene})}} \right)^{\frac{1}{{neg}}}}} & (1) \end{matrix}$

Abridged Best Subset Selection

This method combines a greedy backward search with an exhaustive search. Performing a greedy search alone would be computationally feasible, but because of the nature of the greedy algorithm it does not ensure that the best possible combination of genes for diagnostic purposes is found. On the other hand, because best subset selection is an exhaustive search, it will always select the optimal combination of genes; however, the computational cost of best subset selection increases exponentially, so running it on more than ˜20 genes was infeasible. The Abridged Best Subset Selection (Abridged BSS) is a way to combine the strengths of both of these methods.

First, a greedy backward search on the initial gene list was run. Briefly, the search involves taking the starting gene set and calculating the AUROC after individually removing each of the genes. The search further involves identifying which gene's removal leads to the largest increase in AUROC, and then permanently removing that gene from the set. This same strategy is then applied to the new gene set, once again removing the gene whose exclusion results in the largest increase in AUROC. In a typical greedy backward search, this step would be repeated until a point where removing any gene results in a reduction of AUROC that is greater than some pre-defined threshold is reached. However, in this case, the greedy backward search is simply run until enough genes are eliminated to be able to perform best subset selection (in this case, this cutoff was 20 genes).

The best subset selection can be run on the abridged gene list. Briefly, the diagnostic power of every possible combination of the genes is assessed by calculating the signature scores for each combination and reporting the corresponding AUROC. Next, for every unique number of total genes, the subset of genes that produces the best AUC is reported. This results in a list of the best signatures for each number of total genes, from which the final gene signature can be selected.

Derivation of the 8 Gene Signature Using MANATEE

The Discovery respiratory infection cohorts were analyzed using Multicohort ANalysis of AggregaTed gEne Expression or MANATEE (FIG. 1). MANATEE was developed as a multicohort analysis framework to allow integration of a large number of independent heterogeneous datasets in a single gene expression analyses than was possible with the previous workflow. MANATEE starts by randomly splitting data into discovery and held-out validation. Here 70% of the data was assigned to discovery and the remaining 30% to held-out validation. Next, the discovery and held-out validation data are independently normalize using COCONUT. Within the discovery data, for each gene 5 measures of differential expression between cases and controls were calculated: (1) SAM score (from the Significance Analysis of Microarrays)²⁷, (2) corresponding SAM local FDR, (3) Benjamini-Hochberg FDR corrected P value (from running a t-test)²⁸, (4) effect size, and (5) fold change. The effect size was estimated as Hedges' adjusted g, which accounts for small sample bias. A leave-one-dataset-out (LODO) analysis was also performed, wherein each dataset that accounted for at least 5% of the samples was individually removed from the discovery data, and the differential expression statistics were re-calculated for each iteration of the discovery data with one dataset left out. In order for a gene to be selected by MANATEE, it must not only pass the set thresholds in the statistics calculated in the full discovery data, but it must also pass the thresholds for each iteration of the discovery data with one dataset removed. This prevents any single dataset from exerting too strong of a presence on the selection of genes.

Next, the top 100 genes with the highest SAM score were selected. In order to select only those genes that were highly diagnostic, an Abridged BSS (described above) was performed on these genes. From the results of the Abridged BSS, a 15-gene signature (the signature with the max AUROC) and an 8-gene signature (the smallest signature that was within the 95% CI of the max AUROC signature) were selected to test in Hold-out Validation. Both signatures had equivalent AUROCs, so the 8-gene signature was chosen for next steps.

Results

The systematic search for gene expression microarray or RNA-seq cohorts that profiled patients with intracellular bacterial, extracellular bacterial, or viral infections resulting in febrile symptoms^(3,4) identified 43 whole blood (WB) cohorts and 9 peripheral blood mononuclear cell (PBMC) that met the inclusion criteria.⁵⁻²² The 43 independent WB cohorts were comprised of 1963 non-healthy patient samples (562 extracellular bacterial infections, 320 intracellular bacterial infections, and 1081 viral infections), whereas the 9 independent PBMC cohorts were comprised of 417 non-healthy patient samples (172 extracellular bacterial infections, 11 intracellular bacterial infections, and 234 viral infections). These data included both children and adults from a broad spectrum of geographic regions. 28 WB datasets consisting of 1419 infected samples (348 extracellular bacterial infections, 280 intracellular bacterial infections, and 791 viral infections) were used as discovery cohorts, and the remaining 15 WB datasets consisting of 544 non-healthy samples (214 extracellular bacterial infections, 40 intracellular bacterial infections, and 290 viral infections) were used as independent validation cohorts. Four datasets (3 WB and 1 PBMC) that had no healthy samples, but that had patients with bacterial or viral infections, which were used as independent validation cohorts, were identified.

Selecting Top Differentially Expressed Genes with MANATEE

In order to utilize all of the data that had been collected, a multicohort analysis framework called Multicohort ANalysis of AggregaTed gEne Expression (MANATEE) (FIG. 1) was developed. In this framework, 70% of the data was randomly assigned to the “discovery” cohort and the other 30% as “hold-out validation”. Next, COCONUT normalization was applied across all discovery cohorts.² COCONUT was applied separately to the discovery and held-out validation data. After co-normalization, there were 6086 common genes across all datasets. After calculating differential expression statistics for each gene, the framework involved filtering by selecting the top 100 genes (58 up in bacterial infection, 42 up in viral infection) with the highest SAM (Significance Analysis of Microarrays) score. Using the previously described signature score model^(1,2,5,24,25,) these 100 genes were used to classify samples as having bacterial or viral infections, resulting in an AUROC of 0.874 (95% CI 0.854 to 0.894) in Discovery data.

TABLE 1 (Genes in the final 8-gene signature are underlined) Genes up in bacterial Genes up in viral infection infection EHD1 HERC6 CPD JUP CD44 IFIT1 ZDHHC3 LY6E JAK3 TMEM123 SORT1 MX1 NDST2 NUP205 GAS7 CAPN2 GRB10 TARBP1 IRAK3 IFI44L SOCS3 ICAM2 PADI2 OAS2 ATP9A SUCLG2 UGCG OAS1 ACAA1 RSAD2 SMARCD3 DNMT1 CR1 TLR7 STAT5B ST3GAL5 IL4R DRAP1 MICAL1 IFIT3 ICAM1 GNLY PRKAR2A PRF1 BMX GZMB ALOX5AP MX2 CA4 PTPRO SOD2 IFI44 DACH1 ISG20 MAPK14 IL2RB WDFY3 IFI27 PADI4 RABGAP1L ZNF281 RIN2 VNN1 LY86 HDAC4 BLVRA NARF CD86 NFKBIA ITGA4 IL1R2 FCER1A PGD IFIT2 CDK5RAP2 EPHB1 CD82 SAMD9 FES IFIT5 MKNK1 HESX1 ALCAM CCL8 PHTF1 BCL6 SORL1 PROS1 FLOT2 LIMK2 DYSF ENTPD7 VSIG4 SMPDL3A DAAM2 FKBP5 EBI3 SLC1A3 MMP9 ALPL

Deriving the 8 Gene Signature with MANATEE

The next step involved running an Abridged Best Subset Selection (Abridged BSS) on the list of 100 genes, which consists of first running a greedy backward search to select the top 20 best genes, and then running an exhaustive search on those 20 genes. Running the Abridged BSS on the current gene list allowed identification of most important genes within the signature for distinguishing bacterial and viral infections. From the results of the Abridged BSS, two signatures were selected for testing: the signature that had the maximum AUROC in Discovery [15 genes, AUROC=0.951 (95% CI 0.939 to 0.964)] and the smallest signature that was within the 95% confidence interval of the max AUROC signature [8 genes, AUROC=0.942 (95% CI 0.928 to 0.955); FIG. 2A]. In held-out validation, the 15-gene signature had an AUROC of 0.948 (95% CI 0.926 to 0.969) and the 8-gene signature had an AUROC of 0.947 (95% CI 0.925 to 0.969) (FIG. 2B). Because both signatures had virtually equivalent AUROCs in held-out validation, the smaller 8-gene signature was chosen for further investigation. In this signature, there were 3 genes that were higher in bacterial infections (SMARCD3, ICAM1, EBI3) and 5 genes that were higher in viral infections (JUP, SUCLG2, IFI27, FCER1A, HESX1).

Validating in Independent in Silico Cohorts

In order to verify that the results were broadly applicable and were not simply overfit to the training data, the performance of the 8-gene signature was tested in a series of completely independent cohorts. The 15 WB datasets were normalized with healthy samples that had been left out of discovery and held-out validation using COCONUT. These data included 544 non-healthy samples (214 extracellular bacterial infections, 40 intracellular bacterial infections, and 290 viral infections). The 8-signature had an AUROC of 0.948 (95% CI 0.929 to 0.967), 0.943 (95% CI 0.921 to 0.966), and 0.978 (95% CI 0.945 to 1) for distinguishing all bacterial vs. viral infections, extracellular bacterial vs. viral infections, and intracellular bacterial vs. viral infections, respectively (FIG. 3A). The 8-gene signature was further validated in 3 WB datasets that had both bacterial and viral infections but no healthy samples. In GSE72809 the AUROC was 0.955 (95% CI 0.915 to 0.996), in GSE72810 the AUROC was 0.949 (95% CI 0.882 to 1), in GSE63990 the AUROC was 0.878 (95% CI 0.823 to 0.933), and the summary AUC was 0.914 (95% CI 0.824 to 1) (FIG. 3B).

A similar validation was performed in the 9 PBMC cohorts, which included 417 non-healthy patient samples (172 extracellular bacterial infections, 11 intracellular bacterial infections, and 234 viral infections). After COCONUT normalization of these datasets, it was found that the signature had an AUROC of 0.92 (95% CI 0.891 to 0.949), 0.921 (95% CI 0.891 to 0.95), and 0.906 (95% CI 0.786 to 1) for distinguishing all bacterial vs. viral infections, extracellular bacterial vs. viral infections, and intracellular bacterial vs. viral infections, respectively (FIG. 4A). The 8-gene signature was further validated in a PBMC cohort with bacterial and viral infections but no healthy samples—this cohort was measured on two non-overlapping platforms (GPL570 and GPL2507). Therefore, a validation was done for each platform separately. In GSE6269GPL570 the AUROC was 0.992 (95% CI 0.953 to 1) and in GSE6269GPL2507 the AUROC was 0.938 (95% CI 0.841 to 1) (FIG. 4B).

Validating in Prospective Cohorts

Finally, both the 7-gene and 8-gene signatures were profiled in a prospective cohort of 111 whole blood samples from Nepal using Fluidigm RT-PCR. It contains 25 viral infections, 15 extracellular bacterial infections, and 71 intracellular bacterial infections. Although 7-gene signature distinguished extracellular bacterial infections from viral infections with high accuracy (AUROC=0.886, 95% CI: 0.78-0.99), it had substantially lower accuracy in distinguishing intracellular bacterial infections from viral infections (AUROC=0.78, 95% CI: 0.68-0.88). The 7-gene signature had overall low accuracy in distinguishing bacterial and viral infections (AUROC=0.8, 95% CI: 0.72-0.89) (FIG. 5). In contrast, the 8-gene signature had an AUROC of 0.91 (95% CI 0.816 to 0.1) and 0.915 (95% CI 0.859 to 0.971) for distinguishing viral infections from extracellular and intracellular bacterial infections, respectively. Overall, the 8-gene signature had high accuracy in distinguishing bacterial and viral infection (AUROC=0.914, 95% CI 0.862 to 0.966). Together, these results give high confidence in the diagnostic power of this signature.

Two Gene Combinations

The Area Under the Receiver Operating Curve (AUROC) for each pairwise combination of genes listed in Table 1 was calculated. Table 2 below shows the AUROC for all pairwise combinations of genes that have an AUROC ≥0.80:

TABLE 2 Gene 1 Gene 2 AUROC ICAM1 HERC6 0.89970891 JAK3 JUP 0.88764511 ICAM1 JUP 0.88737838 GRB10 JUP 0.88658108 JAK3 HERC6 0.88606791 JUP SUCLG2 0.88290772 EHD1 JUP 0.88217421 SOCS3 HERC6 0.88200315 HERC6 SUCLG2 0.87954169 PADI2 HERC6 0.87939092 EBI3 HERC6 0.87806596 CD44 JUP 0.87697294 SORT1 HERC6 0.87620174 CPD JUP 0.87618725 ICAM1 HESX1 0.87578135 SOCS3 HESX1 0.87498405 SMARCD3 HERC6 0.87482749 SOD2 HERC6 0.87463034 EHD1 HERC6 0.87398091 NDST2 JUP 0.87397801 SMARCD3 JUP 0.87306475 NDST2 HERC6 0.87303285 ZDHHC3 JUP 0.87271973 LIMK2 HERC6 0.87264145 ACAA1 JUP 0.87184706 CPD HERC6 0.87151944 GRB10 HERC6 0.87084681 SOD2 JUP 0.87078013 NFKBIA HERC6 0.87073954 EBI3 JUP 0.87064097 PADI2 JUP 0.87015969 LIMK2 MX2 0.87008721 MICAL1 JUP 0.86997704 GAS7 JUP 0.86995674 SORT1 JUP 0.86965812 CPD RIN2 0.86911596 UGCG HERC6 0.86802584 JAK3 HESX1 0.86795336 SOCS3 JUP 0.86786058 WDFY3 HERC6 0.86758805 JUP CAPN2 0.86718795 ATP9A JUP 0.86632397 HERC6 JUP 0.86631818 SORT1 HESX1 0.86625729 PRKAR2A JUP 0.86617611 MICAL1 HERC6 0.86564555 WDFY3 JUP 0.865431 ICAM1 MX1 0.86525995 NFKBIA JUP 0.8650454 HERC6 LY86 0.86472938 CD44 HERC6 0.86451194 ACAA1 HERC6 0.86372624 IL4R JUP 0.86329715 JUP TARBP1 0.86325946 SLC1A3 HESX1 0.86296953 SLC1A3 HERC6 0.86293474 ICAM1 LY6E 0.86258103 STAT5B JUP 0.86245347 JAK3 TMEM123 0.86238678 ICAM1 TMEM123 0.86176634 UGCG JUP 0.8615286 BMX HERC6 0.86136045 ICAM1 IFIT1 0.86129376 ZDHHC3 HERC6 0.86127927 CPD TMEM123 0.86126477 PHTF1 HERC6 0.86094585 MAPK14 HERC6 0.86060084 GRB10 HESX1 0.86046748 GAS7 HERC6 0.86043558 LIMK2 MX1 0.86043558 SORT1 RIN2 0.86043269 HERC6 ITGA4 0.86021814 ATP9A HERC6 0.86001519 LIMK2 IFIT1 0.8599717 NDST2 HESX1 0.85995431 PRKAR2A HERC6 0.8596006 CPD HESX1 0.85931357 HERC6 IL2RB 0.85909613 SORT1 MX2 0.85907873 PADI2 HESX1 0.85905844 SMARCD3 HESX1 0.85888158 STAT5B HERC6 0.85884969 LIMK2 HESX1 0.85862065 HERC6 DNMT1 0.85855977 HERC6 TARBP1 0.85854817 FES JUP 0.85798861 UGCG HESX1 0.85797412 SOCS3 MX2 0.85793353 JUP ITGA4 0.85787264 EBI3 HESX1 0.85779146 ALOX5AP HERC6 0.85759431 JUP DNMT1 0.85756532 CPD MX2 0.85744355 JUP NUP205 0.85735367 CDK5RAP2 HERC6 0.85715653 MAPK14 JUP 0.85712173 JAK3 DRAP1 0.85707535 ICAM1 MX2 0.85704055 HERC6 CAPN2 0.85668105 MKNK1 HERC6 0.856481 CD44 TMEM123 0.85639402 JUP HESX1 0.85633024 DACH1 JUP 0.85626645 SOD2 MX2 0.8560983 NARF JUP 0.85591274 JUP ICAM2 0.85579967 JUP RABGAP1L 0.85560832 LIMK2 JUP 0.85548075 HERC6 CD86 0.85539378 IRAK3 HERC6 0.855301 DAAM2 JUP 0.85476754 SOCS3 IFIT1 0.85472115 JUP TMEM123 0.85458199 JUP IL2RB 0.85449501 IL2RB HESX1 0.85441383 DAAM2 HERC6 0.8541326 IL4R HERC6 0.85384267 MKNK1 JUP 0.85381948 CDK5RAP2 JUP 0.85324253 IRAK3 RIN2 0.85314395 ZNF281 JUP 0.85314105 BMX HESX1 0.85303088 SUCLG2 HESX1 0.8529758 EHD1 CAPN2 0.8529729 SMARCD3 LY6E 0.85284823 WDFY3 HESX1 0.85283373 SORL1 JUP 0.85281054 NFKBIA HESX1 0.85275835 FES HERC6 0.85272936 HDAC4 HERC6 0.85264238 HERC6 NUP205 0.85263948 EHD1 LY6E 0.85250902 HERC6 GNLY 0.85248002 SOD2 IFIT1 0.85246843 SORT1 MX1 0.85229737 SOCS3 MX1 0.85226548 PADI2 MX2 0.8521843 HERC6 FCER1A 0.85207703 ALOX5AP JUP 0.85207123 JUP LY86 0.85193496 ICAM1 ISG20 0.85190307 PROS1 HERC6 0.85183059 EHD1 CPD 0.8517784 IRAK3 JUP 0.85174361 SMPDL3A HERC6 0.85169433 IRAK3 HESX1 0.85166533 CR1 JUP 0.85152617 EBI3 LY6E 0.85145079 SORL1 HERC6 0.85136091 PHTF1 HESX1 0.85118406 ACAA1 HESX1 0.85109418 DNMT1 HESX1 0.85105649 BCL6 JUP 0.8510014 MAPK14 HESX1 0.85090863 SLC1A3 JUP 0.85077236 JAK3 MX1 0.85074627 SOD2 HESX1 0.85065929 CD82 JUP 0.85052882 SOCS3 RIN2 0.85038386 SMPDL3A HESX1 0.85037806 BCL6 HERC6 0.85037226 EHD1 HESX1 0.85037226 DYSF HERC6 0.85033167 CPD EPHB1 0.85000986 JUP PRF1 0.84994607 LIMK2 LY6E 0.84974892 SORT1 LY6E 0.84973443 ICAM1 DRAP1 0.84965325 JAK3 LY6E 0.84960976 JAK3 IFIT1 0.84960106 JUP GNLY 0.84949669 JUP GZMB 0.84948509 UGCG IFIT1 0.84947929 JAK3 MX2 0.84934593 SORT1 IFIT1 0.84933723 SOCS3 LY6E 0.84930244 BMX JUP 0.84923576 TARBP1 HESX1 0.84922126 HERC6 ICAM2 0.84921836 PADI2 IFIT1 0.84917777 ICAM1 TLR7 0.84911109 SMPDL3A JUP 0.84901541 EHD1 MX1 0.84891974 ICAM1 OAS2 0.84875158 ZDHHC3 HESX1 0.84865011 JUP PTPRO 0.84858632 FCER1A HESX1 0.84847905 GRB10 TMEM123 0.84845586 EHD1 GRB10 0.84841817 SOD2 MX1 0.84838627 SMARCD3 BLVRA 0.84834278 NFKBIA MX1 0.8482964 EHD1 DRAP1 0.848279 SORT1 BLVRA 0.84808475 CPD IFIT1 0.84805286 MICAL1 HESX1 0.84804996 GAS7 HESX1 0.84801517 DACH1 HERC6 0.84800937 VSIG4 JUP 0.84792529 UGCG MX1 0.8478876 SOD2 TMEM123 0.84746141 NARF HERC6 0.84741792 WDFY3 MX2 0.84741502 NFKBIA IFIT1 0.84738313 CPD RABGAP1L 0.84727296 GRB10 RIN2 0.84723527 NDST2 TMEM123 0.84718018 CR1 HERC6 0.84715699 HDAC4 JUP 0.84713669 PGD JUP 0.84693085 ICAM1 BLVRA 0.846725 SMARCD3 IFIT1 0.84664382 SMARCD3 MX1 0.84659453 EHD1 IFIT1 0.84641478 ATP9A HESX1 0.84629011 ZNF281 HERC6 0.84627851 HERC6 GZMB 0.84599729 PHTF1 JUP 0.8459538 LY6E SUCLG2 0.84589291 EBI3 IFIT1 0.84576245 EHD1 TMEM123 0.84574505 SOD2 LY6E 0.84573055 ICAM1 NUP205 0.84571606 TMEM123 SUCLG2 0.84568997 HERC6 PTPRO 0.84551891 IFIT1 SUCLG2 0.84548122 SORT1 DRAP1 0.84546092 SMARCD3 CAPN2 0.84539134 EHD1 CD44 0.84534205 VSIG4 HERC6 0.84533626 HERC6 PRF1 0.84530146 PADI2 MX1 0.8451739 CD44 HESX1 0.8451449 SORT1 TMEM123 0.84511011 PADI2 TMEM123 0.84507242 PADI2 LY6E 0.84502024 FLOT2 JUP 0.84489847 SLC1A3 IFIT1 0.84487237 GNLY HESX1 0.84485498 MX1 SUCLG2 0.84482599 FLOT2 HERC6 0.8447593 NFKBIA LY6E 0.84459984 EHD1 TARBP1 0.8444027 SOCS3 TMEM123 0.84435921 JUP IFIT1 0.84434761 UGCG MX2 0.84432152 ALOX5AP HESX1 0.84431862 NFKBIA MX2 0.84420265 SMPDL3A RIN2 0.84417655 ENTPD7 JUP 0.84411567 BMX IFIT1 0.84402579 MKNK1 HESX1 0.84401419 PGD HERC6 0.84355611 DYSF MX2 0.84353002 PROS1 JUP 0.84331837 IFI27 FCER1A 0.8431966 SORL1 MX2 0.84318501 CPD CAPN2 0.84314152 JUP ST3GAL5 0.84313572 ALCAM JUP 0.84312122 EBI3 MX1 0.84307194 CD82 HERC6 0.84299656 CPD MX1 0.84297336 JUP CD86 0.84291248 ICAM1 PTPRO 0.84288348 GRB10 DRAP1 0.84270663 FES HESX1 0.84270083 IFIT1 GNLY 0.84258776 EHD1 NDST2 0.84257616 LY86 HESX1 0.84257616 EHD1 NUP205 0.84246019 GRB10 MX2 0.84230073 ICAM1 IFIT5 0.84219056 IL4R MX2 0.84213838 PRKAR2A TMEM123 0.84195862 PROS1 IFIT1 0.84193543 EHD1 MX2 0.84193253 TMEM123 LY86 0.84183395 MAPK14 IFIT1 0.84181656 BCL6 IFIT1 0.84177887 MICAL1 MX2 0.84172088 GAS7 RIN2 0.84170929 BMX LY6E 0.84148314 WDFY3 TMEM123 0.84123091 FES MX2 0.84120771 ICAM1 SAMD9 0.84120771 IFIT1 LY86 0.84119032 ICAM1 RIN2 0.84108595 BMX MX1 0.84101636 MX1 LY86 0.84100187 IRAK3 IFIT1 0.84096998 LY6E FCER1A 0.84073803 DYSF HESX1 0.84071774 LIMK2 OAS1 0.84068295 CPD EBI3 0.84064816 CPD LY6E 0.8404974 ICAM1 OAS1 0.84034953 ALOX5AP IFIT1 0.84034084 SMARCD3 TMEM123 0.84027415 JAK3 NUP205 0.84026256 IL2RB RIN2 0.84023356 SLC1A3 RIN2 0.8400973 UGCG RIN2 0.83986246 EHD1 SUCLG2 0.83979868 SMARCD3 DRAP1 0.83963052 WDFY3 RIN2 0.83961892 UGCG TMEM123 0.83955224 HERC6 HESX1 0.83950875 SOCS3 SAMD9 0.83946526 CPD BLVRA 0.83944207 PRKAR2A HESX1 0.83941887 GAS7 LY86 0.83936379 JUP LY6E 0.8393261 ICAM1 CAPN2 0.83924492 GRB10 IFIT1 0.83917534 DAAM2 HESX1 0.83913475 EHD1 ICAM2 0.83912605 ICAM1 ICAM2 0.83910575 PRF1 HESX1 0.83895499 BCL6 MX2 0.83884482 ZDHHC3 TMEM123 0.83874625 WDFY3 IFIT1 0.83871145 CD44 IFIT1 0.83867376 IL4R IFIT1 0.83864767 ENTPD7 HERC6 0.83862158 PHTF1 IFIT1 0.83861578 HERC6 TMEM123 0.83858099 EHD1 LY86 0.83855489 IFIT1 TARBP1 0.8385462 ICAM1 TARBP1 0.83850851 HDAC4 HESX1 0.83845922 UGCG LY6E 0.83841283 IRAK3 MX2 0.83836354 SLC1A3 MX1 0.83830266 EHD1 GAS7 0.83826497 CPD NDST2 0.83822438 CDK5RAP2 HESX1 0.8381519 CPD NUP205 0.838149 ITGA4 HESX1 0.83811711 ALOX5AP LY6E 0.83791996 JUP MX1 0.83789096 MAPK14 TMEM123 0.83782428 CPD PTPRO 0.83773151 CPD DRAP1 0.83771991 MX1 FCER1A 0.83765612 LY6E LY86 0.83756915 MKNK1 RIN2 0.83756045 CD44 CAPN2 0.83754595 IL4R HESX1 0.83748507 NUP205 HESX1 0.83747057 EHD1 ZDHHC3 0.83743868 NDST2 CAPN2 0.83720384 DYSF IFIT1 0.83718934 GRB10 LY6E 0.83716905 GNLY RIN2 0.83712556 TMEM123 CAPN2 0.83709077 BCL6 MX1 0.83700379 EHD1 JAK3 0.8369603 CR1 HESX1 0.83694001 IFIT1 IL2RB 0.83682404 SMARCD3 MX2 0.83680664 ENTPD7 HESX1 0.83675736 SORL1 IFIT1 0.83675156 ACAA1 CAPN2 0.83674866 SMARCD3 LY86 0.83672836 EHD1 ACAA1 0.83668487 SORT1 SAMD9 0.83667908 EHD1 DNMT1 0.83663849 MX1 TARBP1 0.8365921 ACAA1 TMEM123 0.8365776 SOCS3 OAS1 0.8365718 IFIT1 GZMB 0.83646163 STAT5B MX2 0.83644424 NDST2 NUP205 0.83644134 HDAC4 IFIT1 0.83638335 IFIT1 DNMT1 0.83625868 GAS7 TMEM123 0.83622389 IFIT1 FCER1A 0.83615431 ALOX5AP MX1 0.83607603 MAPK14 LY6E 0.83600935 ICAM2 HESX1 0.83596296 LIMK2 OAS2 0.83584119 IRAK3 MX1 0.83573392 LY6E TARBP1 0.83570782 VSIG4 HESX1 0.83568173 IL4R MX1 0.83566434 SLC1A3 LY6E 0.83565564 SMARCD3 PTPRO 0.83564984 HERC6 RABGAP1L 0.83554837 DYSF JUP 0.83553677 EHD1 EBI3 0.83553677 IFIT1 PRF1 0.83551937 JUP DRAP1 0.83538601 CPD JAK3 0.83536281 NFKBIA TMEM123 0.83536281 FES IFIT1 0.83534542 NDST2 IFIT1 0.83530773 NDST2 MX1 0.83521495 CD44 ICAM1 0.83521205 NDST2 DRAP1 0.83517146 PADI4 HERC6 0.83500041 HERC6 EPHB1 0.83499461 CPD ICAM1 0.83496272 PHTF1 MX1 0.83493952 ALCAM HERC6 0.83485544 STAT5B HESX1 0.83466409 SUCLG2 DRAP1 0.8346235 CPD LY86 0.83454812 MAPK14 MX1 0.83446694 JUP FCER1A 0.83443215 CPD SUCLG2 0.83436257 CR1 IFIT1 0.8342466 BMX MX2 0.83420311 LIMK2 TMEM123 0.83413933 FLOT2 MX2 0.83411033 CD44 MX1 0.83406105 JUP BLVRA 0.83405815 SOCS3 BLVRA 0.83401466 PROS1 HESX1 0.83395667 PHTF1 LY6E 0.83392768 CD44 LY6E 0.83391898 MKNK1 MX2 0.83391898 STAT5B IFIT1 0.83391318 SOCS3 DRAP1 0.83390739 MICAL1 IFIT1 0.83388709 ICAM1 ST3GAL5 0.8338581 DACH1 HESX1 0.83381751 ZDHHC3 DRAP1 0.83378272 CD44 NUP205 0.83373053 TARBP1 RIN2 0.83357687 EHD1 PTPRO 0.83350149 ZNF281 IFIT1 0.83340871 MICAL1 TMEM123 0.83340871 DYSF RIN2 0.83336523 GAS7 IFIT1 0.83335363 GRB10 MX1 0.83328695 EBI3 TMEM123 0.83325215 GRB10 ICAM1 0.83323476 CDK5RAP2 IFIT1 0.83321736 FLOT2 IFIT1 0.83319127 ZDHHC3 IFIT1 0.83317097 JUP TLR7 0.83311299 MAPK14 RIN2 0.8330724 SMPDL3A IFIT1 0.8330579 CD44 SUCLG2 0.83304341 NDST2 LY6E 0.83298542 CD44 RIN2 0.83297093 UGCG OAS1 0.83295063 FES MX1 0.83292744 BCL6 LY6E 0.83290424 MKNK1 IFIT1 0.83289265 EHD1 VSIG4 0.83288395 IL1R2 HERC6 0.83286365 PGD HESX1 0.83284046 ICAM1 CCL8 0.83283466 CD86 HESX1 0.83279407 HERC6 ST3GAL5 0.83275058 ATP9A IFIT1 0.83274478 SORT1 OAS1 0.83272739 STAT5B EBI3 0.83263461 LIMK2 SAMD9 0.83263171 SMARCD3 CD86 0.83262881 PADI4 JUP 0.83259402 HERC6 RIN2 0.83256793 PROS1 MX1 0.83254474 ICAM1 EPHB1 0.83246935 SUCLG2 MX2 0.83242297 DYSF MX1 0.83238528 ACAA1 IFIT1 0.83236208 BCL6 HESX1 0.83214754 NUP205 LY86 0.83204896 MICAL1 MX1 0.83185761 FES LY6E 0.83181412 IFIT1 NUP205 0.83178513 WDFY3 LY6E 0.83174454 TARBP1 MX2 0.83171555 JAK3 RIN2 0.83165176 IRAK3 LY6E 0.83164597 FKBP5 HERC6 0.83162857 IFIT1 ICAM2 0.83161697 STAT5B TMEM123 0.83153579 DNMT1 MX2 0.83148651 NUP205 CAPN2 0.83148361 MICAL1 LY6E 0.83135024 SOCS3 OAS2 0.83122267 IFIT1 CD86 0.83121978 LIMK2 RIN2 0.83121688 ATP9A TMEM123 0.83119948 CD44 NDST2 0.83117919 JUP RIN2 0.83116759 CD44 MX2 0.83104292 EHD1 PRKAR2A 0.83097044 PADI2 DRAP1 0.83083997 SORL1 TMEM123 0.83078489 DYSF LY6E 0.83077329 LY6E IL2RB 0.83075589 LIMK2 IFIT5 0.8307385 PADI2 SAMD9 0.81485927 GAS7 SUCLG2 0.81483898 SORL1 LY86 0.81483028 IRAK3 IFI44L 0.81482738 NFKBIA DRAP1 0.81478679 DNMT1 LY86 0.81476939 STAT5B RIN2 0.81469111 ICAM1 DACH1 0.81463023 CPD PADI2 0.81460414 STAT5B TARBP1 0.81456934 EHD1 CR1 0.81452296 RSAD2 FCER1A 0.81450266 CD44 CD86 0.81448527 CD44 GAS7 0.81440119 EBI3 RSAD2 0.8143403 MICAL1 LY86 0.81429971 IL1R2 LY6E 0.81427942 MX2 ITGA4 0.81425043 SUCLG2 ISG20 0.81421853 SOCS3 EPHB1 0.81421564 ZDHHC3 NUP205 0.81420114 DAAM2 MX2 0.81416635 NFKBIA IFI44 0.81412866 SORT1 ICAM1 0.81411706 MX1 EPHB1 0.81407937 SOD2 IFIT2 0.81406777 SOD2 DRAP1 0.81400689 RSAD2 GNLY 0.81399819 FKBP5 MX1 0.81399239 CD82 MX2 0.81398369 TARBP1 OAS2 0.8139605 EHD1 GNLY 0.81392861 GRB10 SOD2 0.81390831 WDFY3 OAS2 0.81388512 ENTPD7 MX1 0.81387062 ACAA1 PTPRO 0.81385613 NDST2 ACAA1 0.81384743 SMARCD3 ST3GAL5 0.81384453 SUCLG2 OAS1 0.81383003 EHD1 IL4R 0.81382134 PADI2 EPHB1 0.81381844 IRAK3 OAS2 0.81373726 JAK3 SUCLG2 0.81369957 CPD RSAD2 0.81366478 GRB10 RABGAP1L 0.81365898 CD44 TLR7 0.81364158 IL2RB IFI27 0.81362129 IFIT1 IFI27 0.81361839 SOCS3 RABGAP1L 0.81360099 FLOT2 RIN2 0.8135807 OAS1 FCER1A 0.813572 GRB10 OAS2 0.8135633 SORT1 IFIT2 0.81351112 ALPL IFIT1 0.81351112 NDST2 SOD2 0.81349662 STAT5B EPHB1 0.81348502 LIMK2 DRAP1 0.81347632 NFKBIA IFIT3 0.81345313 CDK5RAP2 MX2 0.81339515 GRB10 OAS1 0.81337195 ALCAM LY6E 0.81326758 ACAA1 CD86 0.81323279 BCL6 OAS1 0.81322989 PGD TMEM123 0.81320379 OAS1 GNLY 0.8131632 CPD GZMB 0.81314001 IFIT1 DRAP1 0.81314001 SLC1A3 IFI44L 0.81303854 VNN1 LY6E 0.81296606 CD44 BLVRA 0.81294286 ICAM1 PRF1 0.81291387 ICAM2 SUCLG2 0.81285588 CAPN2 DRAP1 0.81285298 ZNF281 EBI3 0.81285009 CAPN2 DNMT1 0.81282399 TLR7 HESX1 0.8127979 ACAA1 RIN2 0.8127892 TMEM123 PTPRO 0.8127805 PHTF1 OAS2 0.8127776 ICAM1 ALCAM 0.81276311 SLC1A3 BLVRA 0.81267323 MAPK14 OAS2 0.81266453 DACH1 MX2 0.81265873 SMPDL3A MX2 0.81265004 IL4R OAS2 0.81260655 SORT1 EPHB1 0.81258915 WDFY3 OAS1 0.81258625 ZDHHC3 EBI3 0.81258625 JAK3 PROS1 0.81257466 EHD1 RABGAP1L 0.81251377 GRB10 TARBP1 0.81250797 NFKBIA SAMD9 0.81245579 SOD2 RSAD2 0.81243839 EHD1 IRAK3 0.8124094 NDST2 ZNF281 0.812392 SMARCD3 ICAM2 0.8123862 SORT1 IFI27 0.81236591 DNMT1 DRAP1 0.81236011 LIMK2 CCL8 0.81233982 CD44 OAS1 0.81233112 PROS1 MX2 0.81229633 EHD1 NFKBIA 0.81225864 NDST2 SAMD9 0.81224994 VSIG4 CAPN2 0.81222385 CPD ST3GAL5 0.81220355 IFIT1 LY6E 0.81218905 ENTPD7 RIN2 0.81216586 ATP9A NUP205 0.81212237 PADI2 TARBP1 0.81210208 JUP SAMD9 0.81204699 JAK3 PADI2 0.8120296 SOCS3 CAPN2 0.8120267 RSAD2 IL2RB 0.8120209 EHD1 SAMD9 0.81198611 GRB10 SUCLG2 0.81193682 JAK3 STAT5B 0.81191363 EHD1 NARF 0.81184114 PRKAR2A CAPN2 0.81183824 TARBP1 SUCLG2 0.81182375 SMARCD3 EPHB1 0.81176866 EBI3 ICAM2 0.81175996 SUCLG2 RIN2 0.81173097 DNMT1 SAMD9 0.81171068 GAS7 SMARCD3 0.81166139 BMX BLVRA 0.81165269 GNLY SAMD9 0.8116411 JAK3 ICAM1 0.81159761 HERC6 MX2 0.81157151 IL4R OAS1 0.81154542 SOD2 LY86 0.81154542 EBI3 BLVRA 0.81149033 JAK3 IFIT5 0.81148743 UGCG BLVRA 0.81145554 CPD SORT1 0.81139176 PADI2 RABGAP1L 0.81135987 BMX RSAD2 0.81135987 PROS1 RSAD2 0.81135987 UGCG IFIT2 0.81133377 DYSF OAS2 0.81131058 CPD PROS1 0.81128159 CA4 JUP 0.8112468 ENTPD7 LY6E 0.8112352 FKBP5 LY6E 0.8112178 EBI3 IFI44 0.81121201 JAK3 EBI3 0.81119751 SOD2 TARBP1 0.81118301 IRAK3 ICAM1 0.81116272 FES OAS1 0.81116272 TMEM123 MX1 0.81113373 SORT1 CD86 0.81110473 IL1R2 MX1 0.81107284 IL1R2 MX2 0.81106414 ICAM1 RABGAP1L 0.81102645 GRB10 ACAA1 0.81101196 GAS7 GRB10 0.81100326 DYSF RSAD2 0.81097717 GZMB LY86 0.81096557 ZDHHC3 SUCLG2 0.81093948 JAK3 MICAL1 0.81093948 ICAM2 MX2 0.81089599 MAPK14 SAMD9 0.81087279 RIN2 FCER1A 0.8108467 ATP9A BLVRA 0.810838 ICAM1 DAAM2 0.81081481 BMX IFIT5 0.81079161 WDFY3 BLVRA 0.81078581 PADI2 LY86 0.81055967 GZMB PTPRO 0.81052198 EBI3 TARBP1 0.81050749 NDST2 ISG20 0.81049009 CA4 HESX1 0.81048719 GNLY IFI44 0.8104466 TARBP1 RSAD2 0.8104379 ACAA1 SUCLG2 0.81040601 BMX ISG20 0.81037122 VNN1 MX1 0.81031903 DYSF TMEM123 0.81026105 GRB10 PADI2 0.81022626 HDAC4 OAS1 0.81018567 BMX IFI44L 0.81010159 OAS2 GNLY 0.81008419 IRAK3 CCL8 0.8100755 BMX IFI27 0.8100755 ICAM1 ZNF281 0.8100697 CDK5RAP2 OAS2 0.8100523 DNMT1 BLVRA 0.81002621 BCL6 OAS2 0.81000302 PRKAR2A EBI3 0.80999142 BMX CCL8 0.80996532 VSIG4 LY86 0.80996532 DACH1 DRAP1 0.80994503 JAK3 SORT1 0.80994213 EHD1 RSAD2 0.80990734 IRAK3 CAPN2 0.80990444 IL2RB CCL8 0.80990154 NDST2 TLR7 0.80988415 ZDHHC3 NDST2 0.80985805 ALOX5AP OAS2 0.80984646 EHD1 HDAC4 0.80984646 ALCAM RIN2 0.80984356 EBI3 IFIT3 0.80981746 ZDHHC3 GAS7 0.80981746 ISG20 LY86 0.80980877 IFI44L LY86 0.80979137 CPD NARF 0.80971309 SORT1 EBI3 0.80970149 OAS1 PRF1 0.80969859 TLR7 GNLY 0.80965221 PADI4 EBI3 0.80964641 UGCG EBI3 0.80960292 OAS2 IL2RB 0.80954783 GRB10 ISG20 0.80953913 BMX IFIT3 0.80953623 SMARCD3 SUCLG2 0.80953044 GRB10 ICAM2 0.80951304 JUP OAS1 0.80949854 SMPDL3A OAS1 0.80949854 NDST2 OAS1 0.80947535 JAK3 UGCG 0.80945795 NDST2 LY86 0.80945216 SOCS3 PTPRO 0.80937098 ICAM1 PADI4 0.80933039 LIMK2 EPHB1 0.80933039 STAT5B NUP205 0.80931879 NFKBIA CAPN2 0.80931299 PRKAR2A SUCLG2 0.8093014 NUP205 PTPRO 0.8093014 IRAK3 DRAP1 0.8092927 STAT5B DRAP1 0.80926081 GAS7 SOD2 0.80923181 NUP205 RABGAP1L 0.80919992 CR1 OAS1 0.80916803 IL4R EBI3 0.80914484 LY6E ST3GAL5 0.80911874 PRKAR2A RIN2 0.80907815 LIMK2 TLR7 0.80906656 CD44 ICAM2 0.80906076 GAS7 ACAA1 0.80905496 MAPK14 RSAD2 0.80904336 NARF EBI3 0.80903466 ATP9A EBI3 0.80901437 SORL1 NUP205 0.80897668 CDK5RAP2 OAS1 0.80894189 CD44 PROS1 0.80893609 NDST2 PTPRO 0.80893319 UGCG IFI27 0.80891869 ALOX5AP DRAP1 0.8088839 FES OAS2 0.808881 ZDHHC3 PTPRO 0.80879982 GRB10 STAT5B 0.80878823 NARF TMEM123 0.80871864 EBI3 MX2 0.80868675 PROS1 OAS1 0.80865776 CR1 OAS2 0.80857948 TARBP1 PTPRO 0.80856788 MICAL1 ICAM2 0.80855629 ICAM1 GNLY 0.80852729 LY6E TLR7 0.8084867 NFKBIA IFIT5 0.8084838 EHD1 IL2RB 0.80846641 GNLY IFI27 0.80844901 BMX TLR7 0.80839393 IFI44L GNLY 0.80833014 WDFY3 CAPN2 0.80831855 SOCS3 TLR7 0.80828666 HERC6 OAS2 0.80826056 EHD1 PHTF1 0.80825766 FES LY86 0.80825766 GRB10 RSAD2 0.80825186 SORT1 SMARCD3 0.80824027 JAK3 PRKAR2A 0.80823157 CD44 ATP9A 0.80823157 JUP RSAD2 0.80818228 WDFY3 CCL8 0.80815909 SOD2 RABGAP1L 0.80815329 DRAP1 IL2RB 0.8081301 IL2RB BLVRA 0.8081185 VSIG4 PTPRO 0.8081011 DRAP1 LY86 0.80804022 FLOT2 TMEM123 0.80798803 SOD2 IFI44L 0.80794744 MX1 ST3GAL5 0.80793295 MICAL1 PTPRO 0.80791555 CPD IFIT3 0.80789815 FES DRAP1 0.80788946 GAS7 PADI2 0.80785177 UGCG CAPN2 0.80784017 JUP IFI44L 0.80784017 CD44 SAMD9 0.80783437 SOD2 NUP205 0.80782857 SMARCD3 SAMD9 0.80780538 IRAK3 IFIT3 0.80777639 OAS2 HESX1 0.80776189 IRAK3 LY86 0.80775609 PADI2 IFIT5 0.8077358 IFI44 FCER1A 0.80773 ALOX5AP BLVRA 0.8077097 IL1R2 RSAD2 0.80769231 ZDHHC3 SOD2 0.80765752 EHD1 IFIT3 0.80763142 ZDHHC3 ICAM2 0.80757344 NUP205 ICAM2 0.80756764 SORT1 ICAM2 0.80752415 CR1 CAPN2 0.80752125 EBI3 ST3GAL5 0.80751835 CPD IFIT2 0.80749806 TLR7 GZMB 0.80748356 IFI44 IL2RB 0.80746617 ICAM1 BMX 0.80744297 NUP205 TARBP1 0.80738789 TARBP1 SAMD9 0.80737629 MICAL1 BLVRA 0.80735889 JAK3 RABGAP1L 0.8073473 NDST2 PADI2 0.8073241 SORT1 TARBP1 0.8073241 EBI3 SAMD9 0.8073212 GRB10 VSIG4 0.80730961 EHD1 ITGA4 0.80729511 EHD1 IFI44L 0.80727192 RSAD2 LY86 0.80724292 EBI3 CD86 0.80720523 DACH1 EBI3 0.80720233 UGCG EPHB1 0.80715305 HDAC4 OAS2 0.80711246 SOCS3 IFI27 0.80710956 MX1 TLR7 0.80710086 PROS1 IFI27 0.80709216 CD44 ITGA4 0.80708636 SORT1 SUCLG2 0.80704577 IFI44L IL2RB 0.80703708 SUCLG2 RSAD2 0.80703418 MAPK14 EPHB1 0.8069588 PADI4 RIN2 0.8069472 BMX IFI44 0.80691821 TMEM123 FCER1A 0.80691241 SMARCD3 PRKAR2A 0.80689501 NUP205 RIN2 0.80688342 GNLY CCL8 0.80688342 JAK3 VSIG4 0.80687182 ACAA1 TLR7 0.80683703 GRB10 MICAL1 0.80679644 PADI2 SUCLG2 0.80678194 IL4R CAPN2 0.80677034 SUCLG2 EPHB1 0.80675295 PROS1 OAS2 0.80672396 SOD2 IFI44 0.80666597 NFKBIA EPHB1 0.80663988 SMPDL3A DRAP1 0.80663118 UGCG TLR7 0.80661378 STAT5B PTPRO 0.80661088 NFKBIA IFIT2 0.80660219 ACAA1 ICAM1 0.80658769 GRB10 CD86 0.80658769 PADI4 MX2 0.80657609 UGCG SMARCD3 0.8065674 BMX EBI3 0.8065645 SOCS3 NUP205 0.8065616 NDST2 DNMT1 0.8065558 OAS2 GZMB 0.8065471 PADI2 CD86 0.80652971 CPD IFI44 0.80652101 CA4 MX1 0.80652101 TARBP1 CD86 0.80647752 SMARCD3 SORL1 0.80641663 ALOX5AP RSAD2 0.80639054 IRAK3 EBI3 0.80637025 EHD1 CCL8 0.80635575 CPD DNMT1 0.80631226 SUCLG2 CD86 0.80630356 OAS1 GZMB 0.80630066 EHD1 CDK5RAP2 0.80626297 VSIG4 BLVRA 0.80623978 NDST2 GZMB 0.80622238 ATP9A SMARCD3 0.80619629 SOD2 PTPRO 0.8061789 ALOX5AP SAMD9 0.8061731 JAK3 IFI44L 0.8061528 JAK3 DNMT1 0.80613831 UGCG NUP205 0.80610352 CA4 LY6E 0.80609482 IFIT1 ISG20 0.80608612 DAAM2 IFIT1 0.83070951 TMEM123 ICAM2 0.83067761 JAK3 BLVRA 0.83064862 PADI2 RIN2 0.83063992 WDFY3 MX1 0.83061093 SOCS3 CCL8 0.83046597 NDST2 SMARCD3 0.83046307 JAK3 CAPN2 0.83046017 IFIT1 ITGA4 0.83043118 MX1 GNLY 0.83040508 EHD1 CD86 0.83036449 IL1R2 IFIT1 0.8303239 CDK5RAP2 LY6E 0.83023983 JUP ISG20 0.83023983 ALCAM HESX1 0.83010356 PRKAR2A IFIT1 0.83008327 MAPK14 MX2 0.83005137 EHD1 EPHB1 0.8299615 MX1 IL2RB 0.82982813 PROS1 LY6E 0.82981654 CAPN2 HESX1 0.82978754 UGCG OAS2 0.82974985 CPD ACAA1 0.82967737 GZMB HESX1 0.82966867 UGCG SAMD9 0.82965128 ALOX5AP MX2 0.82963678 IFIT1 HESX1 0.82949472 CR1 TMEM123 0.82932946 CPD SAMD9 0.82929177 SOCS3 RSAD2 0.82928887 HERC6 IFIT1 0.82926568 TMEM123 HESX1 0.82921349 ACAA1 BLVRA 0.82910622 SMARCD3 TLR7 0.82908592 ACAA1 LY86 0.82903084 IL1R2 HESX1 0.82900764 DACH1 IFIT1 0.82899894 IL1R2 JUP 0.82899025 LIMK2 IFIT2 0.82899025 CR1 RIN2 0.82895256 EHD1 ATP9A 0.82894386 PGD IFIT1 0.82888008 SORL1 RIN2 0.82887428 SORT1 OAS2 0.82886848 IL4R LY6E 0.82883659 PHTF1 TMEM123 0.8287815 ZNF281 HESX1 0.82865103 DNMT1 RIN2 0.82854376 SORL1 EBI3 0.82849447 SOD2 EPHB1 0.82845678 HDAC4 LY6E 0.82843359 EBI3 OAS2 0.82833501 FLOT2 HESX1 0.82830602 ACAA1 MX2 0.82830022 CPD TARBP1 0.82828573 EHD1 BLVRA 0.82822484 HERC6 BLVRA 0.82822194 NARF HESX1 0.82820745 CPD SMARCD3 0.82819005 SORL1 HESX1 0.82815236 BMX TMEM123 0.82815236 HDAC4 MX1 0.82810597 ICAM1 CD86 0.82807408 PADI2 BLVRA 0.82802479 IFIT1 RIN2 0.82791462 SORL1 MX1 0.82790013 SOD2 OAS1 0.82786823 JUP EPHB1 0.82777836 LY6E DNMT1 0.82773777 GAS7 DRAP1 0.82768848 IRAK3 TMEM123 0.82768558 HDAC4 RIN2 0.82764499 CD44 DRAP1 0.82763629 LY6E ITGA4 0.82763629 GRB10 CAPN2 0.8276102 ZDHHC3 LY6E 0.82758701 SOD2 RIN2 0.82753482 SORT1 CCL8 0.82750583 HDAC4 TMEM123 0.82747104 GRB10 BLVRA 0.82744494 CD82 IFIT1 0.82742465 CPD GRB10 0.82740725 IFIT1 CAPN2 0.82737536 NFKBIA OAS2 0.82736666 IL4R TMEM123 0.82729708 MX1 DNMT1 0.82726519 ACAA1 LY6E 0.82716661 CR1 MX2 0.82715212 CDK5RAP2 MX1 0.82709703 GAS7 MX2 0.82707384 CAPN2 TARBP1 0.82705644 MX1 ITGA4 0.82704774 NARF IFIT1 0.82694627 CR1 LY6E 0.82694337 CD82 HESX1 0.82692308 FLOT2 MX1 0.82687379 LIMK2 IFIT3 0.82687379 CPD CD44 0.82685349 TMEM123 TARBP1 0.8268506 PGD MX2 0.82679261 FES RIN2 0.82675202 HERC6 TLR7 0.82671433 VSIG4 IFIT1 0.82669114 EHD1 ISG20 0.82667374 ZDHHC3 CAPN2 0.82663895 FKBP5 IFIT1 0.82662735 MX2 IL2RB 0.82662155 JAK3 CCL8 0.82660996 NDST2 TARBP1 0.82656357 EHD1 SORT1 0.82653458 NFKBIA OAS1 0.82647079 CR1 MX1 0.82637222 MX1 CD86 0.82636062 ALOX5AP RIN2 0.82635192 LY6E GNLY 0.82634902 ZDHHC3 MX1 0.82630843 EHD1 ICAM1 0.82626784 NDST2 MX2 0.82624465 SMARCD3 OAS1 0.82622436 JAK3 OAS2 0.82614898 TARBP1 DRAP1 0.82610839 JUP MX2 0.82610549 JAK3 NDST2 0.8260417 FLOT2 LY6E 0.82600981 PRKAR2A LY6E 0.82598372 ALOX5AP TMEM123 0.82594313 TARBP1 LY86 0.82592863 SMPDL3A LY6E 0.82592573 GRB10 NUP205 0.82583875 SMARCD3 RIN2 0.82582716 CPD TLR7 0.82578947 JAK3 TLR7 0.82577497 HERC6 LY6E 0.82572858 SOD2 BLVRA 0.82571989 BCL6 TMEM123 0.82568509 PHTF1 RIN2 0.8256793 LY6E HESX1 0.8256503 SOCS3 IFIT5 0.82563871 IFIT1 PTPRO 0.82561551 SORT1 CAPN2 0.82561261 ICAM1 GZMB 0.82559522 SOD2 OAS2 0.82558942 GAS7 LY6E 0.82558652 MX1 ICAM2 0.82556333 DACH1 TMEM123 0.82552274 UGCG RSAD2 0.82543576 SOCS3 IFI44 0.82542706 MX1 PRF1 0.82538067 PADI2 CAPN2 0.82535168 JAK3 PTPRO 0.82531399 CD44 SMARCD3 0.8252676 ATP9A MX1 0.8252676 EHD1 ST3GAL5 0.82516033 GZMB RIN2 0.82509655 STAT5B MX1 0.82500087 ZDHHC3 ICAM1 0.82499217 MKNK1 TMEM123 0.82497768 GAS7 CAPN2 0.82493709 GRB10 LY86 0.82493709 SORT1 RSAD2 0.82490519 ATP9A LY6E 0.82486171 EHD1 UGCG 0.82485591 PRF1 RIN2 0.82472834 STAT5B LY6E 0.82472544 PTPRO HESX1 0.82469935 NDST2 RIN2 0.82465296 LY6E ICAM2 0.82463266 GAS7 BLVRA 0.82462397 JAK3 ISG20 0.82437463 SMPDL3A MX1 0.82430795 LY6E RIN2 0.82425866 MX1 GZMB 0.82424416 LIMK2 RSAD2 0.82417458 SORL1 LY6E 0.82416588 CPD CD86 0.82416298 TMEM123 NUP205 0.82415429 CD44 PTPRO 0.82415139 PADI4 IFIT1 0.8241195 ICAM1 LY86 0.8241108 JAK3 SAMD9 0.8241021 UGCG IFI44 0.82406441 PGD LY6E 0.82403252 MICAL1 DRAP1 0.82400932 CPD ZDHHC3 0.82398033 ZNF281 TMEM123 0.82396294 ST3GAL5 HESX1 0.82389915 JAK3 TARBP1 0.82384117 UGCG CCL8 0.82380638 EHD1 STAT5B 0.82378898 CD44 GRB10 0.82378318 MX1 HESX1 0.823731 GAS7 MX1 0.8237252 CD82 LY6E 0.8237194 ENTPD7 IFIT1 0.82364982 EHD1 GZMB 0.82363242 BMX OAS1 0.82362952 NDST2 SUCLG2 0.82360923 SORT1 LY86 0.82356284 VNN1 HERC6 0.82355414 ZNF281 MX1 0.82351645 ACAA1 MX1 0.82345557 ZDHHC3 MX2 0.82335989 CPD CCL8 0.8233106 LY6E NUP205 0.82329321 SMPDL3A TMEM123 0.82329321 EHD1 SMARCD3 0.82321783 SOD2 ISG20 0.82320333 CD44 PADI2 0.82315694 PGD MX1 0.82313665 ICAM1 RSAD2 0.82307866 EHD1 OAS2 0.82300328 DAAM2 TMEM123 0.82300038 BMX SAMD9 0.8229279 HERC6 MX1 0.82290181 TARBP1 BLVRA 0.82289021 VSIG4 LY6E 0.82288151 LY6E CD86 0.82282353 HERC6 DRAP1 0.82272785 SORT1 ISG20 0.82271626 ATP9A RIN2 0.82270756 CPD OAS1 0.82268726 LY6E CAPN2 0.82268146 IRAK3 BLVRA 0.82256839 TMEM123 DNMT1 0.8225539 PHTF1 MX2 0.82247562 LY6E PRF1 0.82246692 MX1 NUP205 0.82245532 SLC1A3 MX2 0.82245242 EHD1 TLR7 0.82243793 MKNK1 MX1 0.82242343 EBI3 DRAP1 0.82235675 SORL1 EPHB1 0.82229006 SMARCD3 TARBP1 0.82228717 GNLY MX2 0.82226977 CD44 JAK3 0.82225237 MKNK1 LY6E 0.82223788 LIMK2 IFI44 0.82217989 ZDHHC3 LY86 0.8221683 PADI4 HESX1 0.8221683 PRKAR2A MX1 0.8221596 MICAL1 CAPN2 0.82210451 SORT1 IFIT5 0.82209002 GRB10 EBI3 0.82207262 FKBP5 HESX1 0.82206972 UGCG IFI44L 0.82206392 GZMB MX2 0.82197984 MICAL1 TARBP1 0.82197695 ICAM1 PRKAR2A 0.82193056 DAAM2 LY6E 0.82185228 CPD VSIG4 0.82178849 CPD GAS7 0.82178559 ATP9A ICAM1 0.8217653 FES TMEM123 0.8217624 JAK3 CD86 0.8217595 EHD1 RIN2 0.82169572 NDST2 GRB10 0.82166672 MX1 RIN2 0.82163193 GAS7 NUP205 0.82159714 FKBP5 JUP 0.82158555 ICAM1 VSIG4 0.82157105 BMX RIN2 0.82156815 JAK3 OAS1 0.82151596 IFIT1 EPHB1 0.82141159 LY6E GZMB 0.82140869 PADI2 OAS2 0.82126373 IRAK3 OAS1 0.82123474 PADI2 OAS1 0.82121444 ZNF281 LY6E 0.82111297 IFIT1 RABGAP1L 0.82111007 LIMK2 ISG20 0.82110717 IL4R RIN2 0.82104338 ICAM1 IFI44L 0.82104338 EHD1 PADI2 0.82103759 TMEM123 GZMB 0.82093901 SOCS3 IFIT3 0.82092162 ZDHHC3 RIN2 0.82089842 CPD MICAL1 0.82086363 CD44 LY86 0.82080275 JAK3 ICAM2 0.82079405 EBI3 NUP205 0.82072737 SOD2 SAMD9 0.82071577 PRKAR2A DRAP1 0.82070127 LIMK2 IFI44L 0.82068968 CD44 TARBP1 0.82068388 CPD OAS2 0.82066648 EHD1 MICAL1 0.82065488 JAK3 LY86 0.8206085 DACH1 RIN2 0.82055631 MX1 CAPN2 0.82050992 IL1R2 RIN2 0.82044034 EHD1 DAAM2 0.82042874 JAK3 ST3GAL5 0.82042584 EHD1 OAS1 0.82040845 GRB10 SMARCD3 0.82034466 SOCS3 IFI44L 0.82030407 CR1 ICAM1 0.82029828 SORT1 TLR7 0.82028958 ZNF281 MX2 0.82026638 EHD1 ALCAM 0.82024899 ICAM1 IFIT2 0.8202084 ICAM1 IFIT3 0.8201997 MAPK14 OAS1 0.82016491 ICAM1 IFI44 0.82015041 HDAC4 MX2 0.82013302 EBI3 OAS1 0.82012432 CD82 MX1 0.82009533 WDFY3 DRAP1 0.82008953 MAPK14 DRAP1 0.82008953 PROS1 TMEM123 0.82003444 PROS1 RIN2 0.82002285 EHD1 SORL1 0.81997066 BMX DRAP1 0.81996776 MX1 PTPRO 0.81992717 LY6E PTPRO 0.81992137 SMARCD3 OAS2 0.81985759 NDST2 SORL1 0.81985179 CPD ICAM2 0.8198141 ICAM1 SORL1 0.8198112 TMEM123 GNLY 0.8198083 CDK5RAP2 TMEM123 0.81976191 SLC1A3 RSAD2 0.81974452 EPHB1 HESX1 0.81973292 CAPN2 ICAM2 0.81971263 FES BLVRA 0.81970393 NFKBIA RIN2 0.81960825 BCL6 RIN2 0.81957926 SORT1 IFI44 0.81953577 EBI3 PTPRO 0.81953287 DNMT1 RABGAP1L 0.81952707 IFIT1 ST3GAL5 0.81947779 CD44 MICAL1 0.8194198 JUP OAS2 0.81940241 PADI2 PTPRO 0.81937921 SMPDL3A BLVRA 0.81937051 MICAL1 NUP205 0.81936761 CD44 ZDHHC3 0.81934152 GAS7 EBI3 0.81932992 PROS1 RABGAP1L 0.81932123 IFIT1 TLR7 0.81930963 NDST2 OAS2 0.81927774 CPD IFIT5 0.81923425 CD44 OAS2 0.81922265 UGCG IFIT5 0.81919366 SLC1A3 OAS1 0.81910668 SMARCD3 NUP205 0.8190168 DAAM2 MX1 0.81897332 SOD2 IFIT5 0.81896172 GRB10 CCL8 0.81895882 IFI44L FCER1A 0.81893562 EBI3 GZMB 0.81893562 IL2RB SAMD9 0.81889214 PGD RIN2 0.81886894 IFIT1 TMEM123 0.81883995 NDST2 ICAM2 0.81877037 EBI3 RIN2 0.81870079 TMEM123 CD86 0.8186341 CD44 VSIG4 0.81861961 BMX OAS2 0.81859351 SORT1 IFI44L 0.81858192 JAK3 ACAA1 0.81857902 VNN1 IFIT1 0.81848044 OAS2 FCER1A 0.81847754 IRAK3 RSAD2 0.81845145 EHD1 ZNF281 0.81837317 TARBP1 RABGAP1L 0.81836447 EBI3 TLR7 0.81834998 LY6E RABGAP1L 0.81832388 NARF MX1 0.81830359 ICAM1 SUCLG2 0.81829199 SORT1 PTPRO 0.81819921 EBI3 ISG20 0.81818472 OAS2 LY86 0.81816732 GRB10 SAMD9 0.81816442 NDST2 ICAM1 0.81807455 ACAA1 DRAP1 0.81807455 CA4 IFIT1 0.81795278 CPD PRKAR2A 0.81794118 ACAA1 ICAM2 0.81792958 ZDHHC3 JAK3 0.81792668 OAS2 SUCLG2 0.81791219 SOD2 CAPN2 0.8178745 SOD2 TLR7 0.8178658 ATP9A MX2 0.8178542 STAT5B CAPN2 0.81779332 NDST2 BLVRA 0.81778752 SOCS3 ISG20 0.81773823 NDST2 STAT5B 0.81773243 EBI3 CAPN2 0.81770344 DACH1 MX1 0.81769474 ZDHHC3 BLVRA 0.81764546 VNN1 JUP 0.81755268 PRF1 MX2 0.81755268 VSIG4 MX1 0.81752949 IRAK3 IFI27 0.81750049 DACH1 LY6E 0.8174744 ATP9A DRAP1 0.81741641 GAS7 ICAM1 0.81741062 IRAK3 IFI44 0.81731784 EHD1 PROS1 0.81730624 CD44 EBI3 0.81730624 VNN1 HESX1 0.81730044 UGCG DRAP1 0.81729465 PADI2 EBI3 0.81728305 CPD ATP9A 0.81726275 SMARCD3 ISG20 0.81720477 SLC1A3 IFI44 0.81715258 RABGAP1L HESX1 0.81714099 PADI2 ISG20 0.81713229 GRB10 PTPRO 0.81712359 ALCAM IFIT1 0.81711779 DAAM2 RIN2 0.8171004 SLC1A3 OAS2 0.8170975 LY6E EPHB1 0.817083 GAS7 TARBP1 0.81702212 EHD1 WDFY3 0.81701342 SOCS3 IFIT2 0.81699022 UGCG ISG20 0.81692064 GAS7 PTPRO 0.81685686 GAS7 CD86 0.81684526 TMEM123 PRF1 0.81681627 EHD1 SOCS3 0.81674379 ALCAM TMEM123 0.8166945 GRB10 EPHB1 0.8166945 EHD1 SOD2 0.81667131 TMEM123 IL2RB 0.81667131 NDST2 GAS7 0.81663362 UGCG RABGAP1L 0.81657563 VNN1 IFI27 0.81656693 OAS1 IL2RB 0.81654084 SLC1A3 SAMD9 0.81650605 MICAL1 RIN2 0.81649735 GAS7 ICAM2 0.81646256 PADI2 NUP205 0.81645676 PRKAR2A MX2 0.81643647 CAPN2 SUCLG2 0.81643647 PADI4 LY6E 0.81639588 JAK3 GRB10 0.81636109 SORT1 NUP205 0.81632919 SORT1 IFIT3 0.8163089 NARF MX2 0.8162973 IRAK3 SAMD9 0.8162973 ZDHHC3 SMARCD3 0.8162857 CPD ISG20 0.81626541 PADI4 MX1 0.81626541 NARF LY6E 0.81625091 NFKBIA RSAD2 0.81625091 JAK3 EPHB1 0.81619003 PHTF1 SAMD9 0.81615814 VSIG4 TMEM123 0.81614654 CR1 EBI3 0.81611175 UGCG IFIT3 0.81605376 SORL1 RABGAP1L 0.81605376 IFIT1 BLVRA 0.81602767 UGCG ICAM1 0.81601317 JAK3 SMARCD3 0.81601027 ACAA1 TARBP1 0.81600448 NFKBIA IFI44L 0.81597548 STAT5B ICAM1 0.81596389 ICAM1 DNMT1 0.8159291 WDFY3 SAMD9 0.81587111 SORT1 RABGAP1L 0.81586531 DYSF OAS1 0.81586241 VSIG4 RIN2 0.81586241 EHD1 DACH1 0.81585951 HERC6 ISG20 0.81585661 EBI3 IFI44L 0.81583052 PRKAR2A NUP205 0.81574934 CD44 SORT1 0.81572325 EHD1 PRF1 0.81571745 CPD ITGA4 0.81566816 NFKBIA ISG20 0.81564787 JAK3 GAS7 0.81564207 ZNF281 RIN2 0.81562177 ACAA1 NUP205 0.81558698 CD44 ACAA1 0.81558698 LIMK2 BLVRA 0.81556959 SOD2 VSIG4 0.815529 GAS7 EPHB1 0.8155116 LY6E TMEM123 0.81549421 MX1 RABGAP1L 0.81544782 NUP205 MX2 0.81542752 CA4 HERC6 0.81536664 PHTF1 OAS1 0.81535214 TARBP1 OAS1 0.81533475 ATP9A CAPN2 0.81532605 PADI2 TLR7 0.81523907 MAPK14 BLVRA 0.81518109 ICAM1 PROS1 0.81516659 NUP205 SUCLG2 0.8151231 PADI2 CCL8 0.8151144 CD82 TMEM123 0.81505352 SLC1A3 TMEM123 0.81496944 ALOX5AP OAS1 0.81495784 STAT5B LY86 0.81493465 JAK3 ATP9A 0.81489986 SUCLG2 SAMD9 0.81489696 SOD2 IFIT3 0.81488246 TMEM123 ST3GAL5 0.80412912 SMARCD3 IFIT5 0.80412042 SLC1A3 CCL8 0.80411173 IFIT3 GNLY 0.80408273 ATP9A ICAM2 0.80407114 VSIG4 MX2 0.80404214 MICAL1 EBI3 0.80402765 CR1 RSAD2 0.80401025 JUP CCL8 0.80401025 OAS2 ITGA4 0.80399865 NDST2 PROS1 0.80395807 PADI2 IFIT3 0.80392617 IL4R IFI44L 0.80391458 TMEM123 RABGAP1L 0.80389718 SMPDL3A RSAD2 0.80385949 MKNK1 DRAP1 0.80384499 WDFY3 NUP205 0.8038392 IL4R IFI44 0.8038276 HDAC4 RSAD2 0.80379571 GRB10 IFI44L 0.80378991 JAK3 IFIT3 0.80377831 CAPN2 PTPRO 0.80376671 BCL6 IFIT3 0.80374932 JAK3 CR1 0.80372323 SORL1 OAS2 0.80371163 PRKAR2A OAS2 0.80368554 GRB10 SORL1 0.80365364 PGD BLVRA 0.80365364 TARBP1 ISG20 0.80363915 GNLY PTPRO 0.80362755 MAPK14 IFIT3 0.80358406 SORL1 TARBP1 0.80356956 JUP IFIT5 0.80356377 ICAM2 RIN2 0.80356377 ACAA1 EBI3 0.80355217 SMARCD3 IFIT3 0.80352898 IFIT1 CCL8 0.80352608 BCL6 RSAD2 0.80349418 PADI2 ST3GAL5 0.80349128 FKBP5 MX2 0.80348549 JAK3 IL4R 0.80347389 NDST2 EBI3 0.80347389 IFI44L GZMB 0.80346519 ICAM1 NARF 0.80345359 NDST2 PRKAR2A 0.8034391 PHTF1 IFIT5 0.80340141 PADI2 ICAM2 0.80338401 CPD PRF1 0.80336082 CPD UGCG 0.80333472 ACAA1 OAS2 0.80332603 ATP9A OAS2 0.80328254 TLR7 IL2RB 0.80324775 UGCG SUCLG2 0.80324195 MICAL1 TLR7 0.80323325 CPD DACH1 0.80321296 GRB10 IFI44 0.80318106 CD44 EPHB1 0.80318106 ATP9A OAS1 0.80317527 DAAM2 IFI27 0.80317237 CPD GNLY 0.80317237 EHD1 IFIT5 0.80316947 PADI4 TMEM123 0.80316947 WDFY3 EPHB1 0.80316077 CPD FCER1A 0.80315787 MX1 BLVRA 0.80313178 NARF CAPN2 0.80310278 CA4 RIN2 0.80309989 SORT1 PADI2 0.80308829 IL4R RSAD2 0.8030535 CPD ALCAM 0.80299261 CAPN2 LY86 0.80298681 ATP9A SAMD9 0.80297812 SMPDL3A IFI44L 0.80297232 EBI3 PRF1 0.80292593 IRAK3 IFIT5 0.80292013 FCER1A CCL8 0.80291433 NDST2 CR1 0.80290274 MAPK14 TLR7 0.80289404 IFI44 LY86 0.80288244 NDST2 MICAL1 0.80286215 JUP IFI44 0.80285925 DACH1 SUCLG2 0.80285055 SMPDL3A OAS2 0.80283895 SLC1A3 IFIT3 0.80282736 FES CAPN2 0.80278097 NDST2 UGCG 0.80276937 SUCLG2 LY86 0.80275777 PADI2 ATP9A 0.80273168 GRB10 PRKAR2A 0.80269399 SLC1A3 IFIT5 0.80269109 TLR7 PRF1 0.80269109 GAS7 MICAL1 0.80267949 PRF1 IFI44 0.8026331 UGCG GZMB 0.80262441 JAK3 GZMB 0.80258962 IFIT1 MX2 0.80256352 PRF1 SAMD9 0.80255772 DYSF IFI44 0.80255482 BCL6 IFI44 0.80253453 CPD IL4R 0.80250844 SMARCD3 IFI44 0.80246495 CD44 ISG20 0.80246495 MAPK14 EBI3 0.80245625 ISG20 FCER1A 0.80244465 GAS7 OAS2 0.80244175 DYSF CCL8 0.80243596 ZDHHC3 MICAL1 0.80240986 IL4R NUP205 0.80238667 HDAC4 IFI44L 0.80238087 PROS1 EBI3 0.80233158 PROS1 TLR7 0.80230549 ALOX5AP ISG20 0.80229389 PRF1 LY86 0.8022765 CR1 IFI44L 0.8022562 HDAC4 TLR7 0.8022475 OAS1 LY86 0.80223881 CD44 IFI44L 0.80221271 BMX IFIT2 0.80220401 CD44 ALOX5AP 0.80218952 ZDHHC3 TARBP1 0.80218372 ALOX5AP EPHB1 0.80215183 SOD2 CCL8 0.80214893 IRAK3 ISG20 0.80208804 PRF1 IFI27 0.80208515 CPD SOCS3 0.80207645 SORL1 FCER1A 0.80207355 CDK5RAP2 IFI44L 0.80204456 HDAC4 BLVRA 0.80203586 JUP IFIT3 0.80202716 CD44 RSAD2 0.80201556 MAPK14 PTPRO 0.80200976 EHD1 IFI44 0.80200687 SORT1 ZNF281 0.80199817 DNMT1 EPHB1 0.80199237 CD44 IFI44 0.80196048 WDFY3 RSAD2 0.80194888 NUP205 BLVRA 0.80194888 ALOX5AP CCL8 0.80193148 SORT1 PRKAR2A 0.80192859 SMARCD3 STAT5B 0.80192859 HERC6 CCL8 0.80191989 JAK3 IRAK3 0.80191119 ZDHHC3 STAT5B 0.8018706 EHD1 ENTPD7 0.8018677 SORT1 STAT5B 0.8018677 IFIT3 FCER1A 0.801859 TARBP1 CCL8 0.8018561 PROS1 IFI44 0.80183871 BCL6 EPHB1 0.80183291 IL4R BLVRA 0.80177492 WDFY3 ISG20 0.80177203 PHTF1 BLVRA 0.80173434 GAS7 PROS1 0.80172274 CD44 NARF 0.80171984 ZDHHC3 OAS1 0.80170824 SLC1A3 IFI27 0.80170534 STAT5B OAS2 0.80166765 GZMB BLVRA 0.80166185 GRB10 PROS1 0.80165606 CD44 PRKAR2A 0.80163576 NDST2 IFI44L 0.80162126 VNN1 IFI44L 0.80160097 MICAL1 EPHB1 0.80159807 HDAC4 IFI44 0.80158357 OAS2 CD86 0.80156908 ALOX5AP GZMB 0.80156328 ALOX5AP IFIT3 0.80155748 PRKAR2A ICAM2 0.80154009 NARF TARBP1 0.8014821 DAAM2 DRAP1 0.8014705 ACAA1 ST3GAL5 0.8014676 BMX CAPN2 0.80141252 MICAL1 OAS1 0.80140672 ALOX5AP CAPN2 0.80133424 PGD OAS2 0.80132844 PHTF1 TLR7 0.80131684 NFKBIA GZMB 0.80130525 ICAM2 DRAP1 0.80129945 BMX EPHB1 0.80127915 PROS1 IFIT3 0.80126755 VNN1 RSAD2 0.80125886 NFKBIA BLVRA 0.80124726 SORT1 VSIG4 0.80122697 RSAD2 CD86 0.80120667 WDFY3 TLR7 0.80118928 BCL6 IFIT2 0.80118638 OAS1 ITGA4 0.80118348 ISG20 HESX1 0.80113709 CA4 EBI3 0.80112259 TMEM123 RIN2 0.80111389 EHD1 SMPDL3A 0.8010994 TARBP1 IFI44 0.8010994 IFIT3 IL2RB 0.8010965 ALOX5AP IFI44L 0.8010849 BMX PTPRO 0.8010849 CDK5RAP2 BLVRA 0.801082 SMPDL3A IFI44 0.8010762 SMPDL3A SAMD9 0.80106171 IL1R2 OAS1 0.80104141 SOD2 ST3GAL5 0.80104141 CR1 PTPRO 0.80103851 HDAC4 CAPN2 0.80102402 TARBP1 IFI27 0.80099792 ZDHHC3 RABGAP1L 0.80099213 ISG20 IL2RB 0.80099213 LY6E MX1 0.80098343 GAS7 CCL8 0.80097473 TMEM123 DRAP1 0.80092834 TMEM123 ITGA4 0.80091964 ATP9A ACAA1 0.80089645 ALPL LY6E 0.80087905 GRB10 ZNF281 0.80087326 STAT5B TLR7 0.80087326 GRB10 GZMB 0.80084136 HERC6 OAS1 0.80080947 ATP9A RABGAP1L 0.80076888 GAS7 PRKAR2A 0.80076308 IFI44L RIN2 0.80075729 NFKBIA NUP205 0.80075729 SORT1 ACAA1 0.80074569 MKNK1 OAS2 0.80073119 IFI27 HESX1 0.80073119 WDFY3 TARBP1 0.8007196 ZNF281 EPHB1 0.8006935 BCL6 SAMD9 0.80067611 FLOT2 BLVRA 0.80064711 SORT1 NDST2 0.80062972 PADI2 IFI44 0.80062682 FKBP5 RIN2 0.80053984 RSAD2 HESX1 0.80052824 SUCLG2 IFI44 0.80047026 IL4R EPHB1 0.80047026 ZDHHC3 PADI2 0.80045866 IL1R2 IFI44L 0.80044707 ACAA1 OAS1 0.80041807 IL4R SUCLG2 0.80040358 SORT1 GRB10 0.80039778 GRB10 IFIT5 0.80038618 DNMT1 PTPRO 0.80036299 DRAP1 HESX1 0.80035719 VNN1 TMEM123 0.80035429 NFKBIA TLR7 0.80034269 IL1R2 IFI44 0.8003253 DACH1 BLVRA 0.8003021 HERC6 RSAD2 0.80025571 SORT1 SOD2 0.80025282 SMARCD3 GZMB 0.80023542 SMARCD3 DACH1 0.80023542 HDAC4 TARBP1 0.80022672 SMARCD3 ICAM1 0.80019483 IL2RB IFIT5 0.80018323 DAAM2 OAS2 0.80016874 NDST2 RSAD2 0.80016294 TARBP1 IFIT3 0.80012815 IFI44L ITGA4 0.80011945 STAT5B RABGAP1L 0.80011655 CD44 ST3GAL5 0.80008466 GAS7 RABGAP1L 0.80008176 VSIG4 SUCLG2 0.80007886 IL1R2 TMEM123 0.80005856 MAPK14 CAPN2 0.80004697 SMPDL3A IFI27 0.80002087 PRF1 PTPRO 0.80001798 ZDHHC3 SAMD9 0.80001508 FLOT2 OAS1 0.80566863 SMARCD3 RSAD2 0.80562224 ALCAM MX1 0.80560194 GRB10 TLR7 0.80559904 SMARCD3 EBI3 0.80557585 HDAC4 SAMD9 0.80557295 RSAD2 PRF1 0.80556135 PHTF1 RSAD2 0.80554686 GRB10 IFI27 0.80553236 PHTF1 IFI44 0.80551207 OAS1 DNMT1 0.80547728 DYSF BLVRA 0.80541929 EBI3 IFI27 0.80540189 IRAK3 IFIT2 0.80537 NDST2 CD86 0.80532362 ZDHHC3 OAS2 0.80531782 ALPL HERC6 0.80530912 SUCLG2 TLR7 0.80530622 JAK3 RSAD2 0.80530332 ICAM1 EBI3 0.80529462 EHD1 BMX 0.80526563 CD44 DNMT1 0.80526273 JAK3 PADI4 0.80523954 MKNK1 BLVRA 0.80521634 MAPK14 IFI44L 0.80508588 EBI3 IFIT5 0.80505108 ATP9A LY86 0.80502789 ZNF281 SUCLG2 0.80501339 CR1 LY86 0.8049989 RSAD2 DNMT1 0.8049757 NDST2 VSIG4 0.80496701 PGD OAS1 0.80495541 EBI3 GNLY 0.80495541 WDFY3 EBI3 0.80495251 CR1 EPHB1 0.80493801 HDAC4 DRAP1 0.80492642 DYSF IFI44L 0.80491772 PRF1 BLVRA 0.80491482 EHD1 MAPK14 0.80488873 TMEM123 EPHB1 0.80481914 ATP9A PTPRO 0.80479885 OAS2 DNMT1 0.80478725 PHTF1 IFI44L 0.80477276 EHD1 ALOX5AP 0.80474666 PADI2 IFI44L 0.80474666 ATP9A SUCLG2 0.80474666 MICAL1 CD86 0.80473217 HERC6 IFI27 0.80471477 SUCLG2 CCL8 0.80468288 SORL1 SUCLG2 0.80467998 CR1 DRAP1 0.80466258 GZMB CD86 0.80465969 SORT1 GAS7 0.80464809 TARBP1 GZMB 0.80463069 BCL6 IFI44L 0.8046162 CD44 SOD2 0.804593 JAK3 IFI44 0.80457851 EHD1 FCER1A 0.80457561 FCER1A SAMD9 0.80455241 IL4R SAMD9 0.80454661 MICAL1 ST3GAL5 0.80452632 MICAL1 OAS2 0.80451762 IFI44L PRF1 0.80450602 SORT1 GZMB 0.80449443 CD44 RABGAP1L 0.80449153 CPD SOD2 0.80448863 ALCAM SUCLG2 0.80448573 SUCLG2 PTPRO 0.80445964 JAK3 SORL1 0.80441905 NFKBIA CCL8 0.80441325 MX2 FCER1A 0.80440165 RIN2 HESX1 0.80439875 SUCLG2 IFIT3 0.80439585 TMEM123 BLVRA 0.80438136 DRAP1 GNLY 0.80436106 OAS2 PRF1 0.80432627 CPD NFKBIA 0.80431757 DYSF SAMD9 0.80429728 IRAK3 RABGAP1L 0.80426829 FLOT2 OAS2 0.80425089 VSIG4 DRAP1 0.80423929 VSIG4 CD86 0.8042219 STAT5B SUCLG2 0.8042219 CD44 BMX 0.804219 JAK3 SOD2 0.8042132 JAK3 ALCAM 0.8041987 IFIT1 MX1 0.80417551 LY86 SAMD9 0.80415232 PHTF1 ISG20 0.80414362 RSAD2 ITGA4 0.80413782 EHD1 MKNK1 0.80594696 CPD IFI44L 0.80594116 MX2 LY86 0.80589767 CR1 BLVRA 0.80588317 SORL1 CAPN2 0.80587157 GNLY BLVRA 0.80587157 LY6E BLVRA 0.80586868 IFI44L SUCLG2 0.80586578 SORT1 ST3GAL5 0.80586288 TARBP1 IFI44L 0.80585998 JAK3 NARF 0.80585418 GAS7 TLR7 0.80584838 ENTPD7 TMEM123 0.80583968 NUP205 CD86 0.80582519 RSAD2 GZMB 0.8057875 PROS1 IFI44L 0.8057759 SOD2 CD86 0.8057556 VNN1 RIN2 0.80572661 CPD STAT5B 0.80570922 ATP9A TARBP1 0.80570632 IL4R TARBP1 0.80568602 NDST2 ATP9A 0.80608032 TARBP1 ICAM2 0.80607742 PADI2 RSAD2 0.80605423 SMARCD3 IFI44L 0.80601074 MAPK14 IFI44 0.80595565

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That which is claimed is:
 1. A method of analyzing a sample, the method comprising: (a) obtaining a sample of RNA from a subject; and (b) measuring the amount of RNA transcripts encoded by JUP, SUCLG2, IFI27, FCER1A, HESX1, SMARCD3, ICAM1, and EBI3 in the sample, to produce gene expression data.
 2. The method of claim 1, wherein the measuring step is done by RT-PCR.
 3. The method of claim 1, wherein the measuring step is done using a quantitative isothermal amplification method.
 4. The method of claim 1, wherein the measuring step is done by sequencing.
 5. The method of claim 1, wherein the measuring step is done by labeling the RNA or cDNA made from the same and hybridizing the labeled RNA or cDNA to a support.
 6. The method of any prior claim, wherein the sample comprises RNA isolated from whole blood, white blood cells, neutrophils, peripheral blood mononuclear cells (PBMCs), or buffy coat.
 7. The method of claims 1-6, further comprising: (c) based on the gene expression data, providing a report indicating whether the subject has a viral infection or a bacterial infection, wherein: (i) increased JUP, SUCLG2, IFI27, FCER1A, HESX1 expression indicates that the subject has a viral infection; and (ii) increased SMARCD3, ICAM1, EBI3 indicates that the subject has a bacterial infection.
 8. A method for treating a subject, comprising: (a) receiving a report indicating whether the subject has a viral infection or a bacterial infection, wherein the report is based on the gene expression data obtained by measuring the amount of RNA transcripts encoded by JUP, SUCLG2, IFI27, FCER1A, HESX1, SMARCD3, ICAM1, and EBI3, and (b) identifying the patient as having increased JUP, SUCLG2, IFI27, and FCER1A, and HESX1 expression; and treating the subject with anti-viral therapy; or (c) identifying the patient as having increased SMARCD3, ICAM1, EBI3 expression; and treating the subject with an anti-bacterial therapy.
 9. The method of claim 8, wherein step (b) comprises administering an anti-viral agent to the subject.
 10. The method of claim 8, wherein step (c) comprises administering an antibiotic to the subject.
 11. A kit comprising reagents for measuring the amount of RNA transcripts encoded by JUP, SUCLG2, IFI27, FCER1A, HESX1, SMARCD3, ICAM1, and EBI3.
 12. The kit of claim 11, wherein the reagents comprise, for each RNA transcript, a sequence-specific oligonucleotide that hybridizes to the transcript.
 13. The kit of claim 12, wherein sequence-specific oligonucleotide is biotinylated and/or labeled with an optically-detectable moiety.
 14. The kit of claim 11, wherein the reagents comprises, for each RNA transcript, a pair of PCR primers that amplify a sequence from the RNA transcript, or cDNA made from the same.
 15. The kit of claim 11, wherein the reagents comprise multiple reaction vessels, each comprising at least one sequence-specific isothermal amplification primer that hybridizes to the transcript, or cDNA made from the same. 